Liquid pumping cassettes and associated pressure distribution manifold and related methods

ABSTRACT

A fluid-handling cassette comprising a plurality of diaphragm valves and pumps is configured to have its actuation ports located along a thin or narrow edge of the cassette. Actuation channels within the cassette lead from the actuation ports to actuation chambers of the valves and pumps in a space between plates that comprise the cassette. The individual plates have a nominal thickness that is sufficient to provide a rigid ceiling for the actuation channels, but sufficiently thin to minimize the overall thickness of the cassette. The cassette can be plugged into or unplugged from an actuation receptacle or a manifold by its narrow edge. A plurality of such cassettes can be stacked together or spaced apart from each other to form a cassette assembly, providing for a convenient way to install and remove the cassette assembly from its actuation receptacle. The arrangement allows for an improved way of connecting a complex cassette assembly to its associated pressure distribution manifold without the use of a plurality of flexible connecting tubes between the two.

CROSS-REFERENCE TO RELATED APPLICATION

The present application is a Non-Provisional application which claimspriority from U.S. Provisional Patent Application Ser. No. 62/650,820,filed Mar. 30, 2018 and entitled LIQUID PUMPING CASSETTES AND ASSOCIATEDCOMPONENTS (Attorney Docket No. W03), and U.S. Provisional PatentApplication Ser. No. 62/745,807, filed Oct. 15, 2018 and entitled LIQUIDPUMPING CASSETTES AND ASSOCIATED PRESSURE DISTRIBUTION MANIFOLD(Attorney Docket No. Y32), which are hereby incorporated herein byreference in their entireties.

FIELD OF THE INVENTION

This disclosure generally relates to improvements in the design andconstruction of fluid pumping or mixing cassettes, cassette assemblies,their constituent parts, and associated devices.

BACKGROUND

Liquid-handling cassettes comprising diaphragm pumps and/or valves canbe actuated fluidically (either hydraulically or pneumatically). In someexamples, a cassette is designed to be fluidically connected to apneumatic actuation manifold having electromechanical valves thatselectively distribute positively or negatively pressurized gas or airto the cassette. A programmable electronic controller can be used tocontrol the electromechanical valves to selectively deliver positive ornegative pneumatic pressure to various pumps or valves of the cassettein a pre-determined manner.

Some fluid-handling cassettes can be substantially planar in shape,having a broad side flanked by a thin or narrow side having a relativelysmaller thickness that the overall broad side dimensions of thecassettes. Liquid inlet and outlet ports can be incorporated into theedge or thin side of the cassette. But in many of these devices,actuation ports for the cassette have been located on the face or broadside of the cassette directly over the actuation chambers of the pumpsor valves being controlled. This generally provides the shortest routefor an actuation channel in the cassette from an external cassetteactuation port to the actuation chamber and diaphragm of a pump or valvein the cassette. Furthermore, in many cases the pumping or valvestations or regions of the cassette—comprising either the actuationchamber on one side or the liquid carrying chamber on the opposingside—may be defined by spheroid or hemi-spheroid chamber walls thatextend above the plane of the cassette face, which makes the overallcassette thicker than desirable in some applications. In other cases, apump module may comprise a set of blocks sandwiched or laminatedtogether, with the pneumatic actuation channels or fluid channelsembedded within one or more of the blocks. This arrangement may alsoresult in an overall device thickness greater than desirable for certainapplications. Some applications may require a plurality of fluidhandling cassettes to be mounted next to each other in tight spaces. Inthese cases, it may be desirable to position a number of cassettesadjacent to one another, to stack them against each other, or at leastto place their broad sides face-to-face in close proximity. Reducing orminimizing the thickness of the individual cassettes constituting theseassemblies may be particularly desirable.

It may be advantageous to arrange for a pump cassette to plug directlyinto its associated pressure distribution manifold (for example, amanifold that selectively delivers pneumatic pressure to the pumpcassette under control of an electronic controller). In previouslydisclosed embodiments of a hemodialysis system using pneumaticallyactuated self-contained pump cassettes, the pump cassettes wereconnected to a corresponding pneumatic manifold via flexible tubes,which has led to significant challenges during assembly and in theiroperation. If a pump cassette can be located close to its associatedmanifold, a direct plug-in connection between the two would havesubstantial advantages. Under these circumstances, it would beparticularly advantageous to have a compact manifold that allows for adirect interface to a pump cassette, arranged in such a manner as toallow the cassette or cassette assembly to be plugged into and unpluggedfrom the actuation ports of the manifold with minimal effort.

In the design and operation of a pneumatic distribution manifold, theability to use binary pressure control valves rather than continuouslyvariable orifice valves would also provide significant advantages inboth cost and reliability. But in this case, the control of pressuredelivery to individual cassette pumps or valves by binary pressurecontrol valves poses additional challenges that must be overcome. Asufficiently robust electronic controller can be programmed to usecontrol algorithms to control the frequency and duration of binary valveactuation to achieve precise control of associated pneumaticallyactuated pumps or valves.

SUMMARY

In an embodiment, a pump and/or valve cassette has a relatively planarshape, with a broad side flanked by a thinner narrow side or edge. Itcomprises a midplate positioned between two outer plates: a first outerplate facing a first side of the midplate, and a second outer platefacing an opposing second side of the midplate. The first outer plate isspaced apart from the midplate to form a first inter-plate space. Thesecond outer plate is spaced apart from the midplate to form a secondinter-plate space. The thickness of the first and second outer plates islimited to a thickness sufficient to impart rigidity to the plate and toprovide a sealing surface against opposing channel walls of either sideof the midplate. In some embodiments, the thickness of each outer plate,together with the thickness of the midplate between them, define theoverall thickness of the cassette. In other embodiments, liquid inletand outlet ports jut out from an outer face of the cassette, which addsto the overall thickness of the cassette. The cassette can include oneor more pump stations or regions and two or more valve stations orregions. The number of pump or valve stations and their size maydetermine the overall broad-side dimensions of the cassette. The strokevolume of an on-board pump is a function of the diameter of a pumpstation and its associated diaphragm and the depth of excursion of thediaphragm defined by the depth of channel walls of the midplate, andthis will in turn determine the thickness of the cassette as well as itsbroad-side dimension. For any given pump or valve station, the midplatecomprises an actuation side and an opposing liquid side, with theactuation side holding a pump or valve diaphragm. Actuation channels inthe cassette to the respective pump or valve stations can be containedwithin midplate channels of the first inter-plate space and rungenerally parallel to the broad side of the cassette. Liquid channels inthe cassette can be contained within midplate channels of the secondinter-plate space and also generally run parallel to the broad side ofthe cassette, except in some cases where the liquid channels connect toan inlet or outlet of the cassette. In this arrangement, the first andsecond outer plates function primarily to provide a roof or limit wallover the respective actuation and liquid carrying valve or pump regions.

In an embodiment, a fluid handling cassette can comprise a mid-platepositioned between a first plate and a second plate, the plates having alength, a width and a plate thickness, a first side of the mid-plateopposing the first plate and a second side of the mid-pate opposing thesecond plate. The first plate is spaced apart from the mid-platedefining a width of a first inter-plate space, and the second platespaced apart from the mid-plate defining a width of a second inter-platespace. An edge of the cassette has a cassette thickness defined by thethickness of each plate plus the width of the first and secondinter-plate spaces, and a face of the cassette being defined by thelength and width of the first or second plate. The mid-plate cancomprise a pump station defined by a pump diaphragm and the first sideof the mid-plate, said pump diaphragm seated against the first side ofthe midplate and having an excursion range defined by the width of thefirst inter-plate space. A pump actuation channel runs parallel to theface of the cassette in the first inter-plate space connecting a pumpactuation chamber bounded by the first plate and the pump diaphragm witha cassette pump actuation port located within the first inter-platespace at a first edge of the cassette. A first and a second pump fluidport in the pump station may fluidly connect a respective first andsecond fluid channel in the second inter-plate space to a pumpingchamber defined by the pump diaphragm and the first side of themid-plate. A pump fluid port in the pump station fluidly may connect afluid channel in the second inter-plate space with a pumping chamberdefined by the pump diaphragm and the first side of the mid-plate.Alternatively, there may be an aperture in the mid-plate at the pumpstation, the aperture allowing the pump diaphragm to move from the firstplate to the second plate when actuated by positive or negative pressuredelivered through the pump actuation channel. The plates (first,mid-plate and second) are generally insufficiently thick to allow fluidor actuation channels to travel within the plates in a directionparallel to the face of the cassette. A fluid channel may run in thesecond inter-plate space, and fluidly connect to a pumping chamberdefined by the pump diaphragm and the first side of the mid-plate, theconnection being made through one or more pump fluid ports in themid-plate, so that the fluid channel runs parallel to the face of thecassette in the second inter-plate space connecting the pumping chamberwith a cassette fluid port located within the second inter-plate spaceat the first edge or at a second edge of the cassette.

In an embodiment, a fluid handling cassette may comprise a mid-platepositioned between a first plate and a second plate, the plates having alength, a width and a plate thickness, a first side of the mid-plateopposing the first plate and a second side of the mid-pate opposing thesecond plate. The first plate is spaced apart from the mid-platedefining a width of a first inter-plate space, and the second plate isspaced apart from the mid-plate defining a width of a second inter-platespace. An edge of the cassette has a cassette thickness defined by thethickness of each plate plus the width of the first and secondinter-plate spaces, and a face of the cassette is defined by the lengthand width of the first or second plate. The mid-plate may comprise avalve station defined by a valve diaphragm and the first side of themid-plate, the valve diaphragm seated against the first side of themidplate and having an excursion range defined by the width of the firstinter-plate space. And a valve actuation channel may run parallel to theface of the cassette in the first inter-plate space connecting a valveactuation chamber bounded by the first plate and the valve diaphragmwith a cassette valve actuation port located within the firstinter-plate space at a first edge of the cassette. A first and secondvalve fluid port in the valve station fluidly may fluidly connect arespective first and second fluid channel in the second inter-platespace to a valve fluid chamber defined by the valve diaphragm and thefirst side of the mid-plate. One or both valve fluid ports may comprisea raised valve seat to seal the valve diaphragm over the first or secondvalve fluid port when positive pressure is applied to the valvediaphragm via the valve actuation channel. The first fluid channel isfluidically isolated from the second fluid channel other than throughthe first and second valve fluid ports. A fluid channel may run in thesecond inter-plate space, and fluidly connect to a valve fluid chamberdefined by the valve diaphragm and the first side of the mid-plate, theconnection being made through two valve fluid ports in the mid-plate, sothat the fluid channel runs parallel to the face of the cassette in thesecond inter-plate space connecting the valve fluid chamber with acassette fluid port located within the second inter-plate space at thefirst edge or at a second edge of the cassette.

In another embodiment, a fluid handling cassette may comprise amid-plate positioned between a first plate and a second plate, theplates having a length, a width and a plate thickness, a first side ofthe mid-plate opposing the first plate and a second side of the mid-pateopposing the second plate. The first plate is spaced apart from themid-plate defining a width of a first inter-plate space, and the secondplate is spaced apart from the mid-plate defining a width of a secondinter-plate space. An edge of the cassette has a cassette thicknessdefined by the thickness of each plate plus the width of the first andsecond inter-plate spaces, and a face of the cassette being defined bythe length and width of the first or second plate. The mid-plate maycomprise a pump station defined by a pump diaphragm and the first sideof the mid-plate, the pump diaphragm seated against the first side ofthe mid-plate and having an excursion ranged defined by the width of thefirst inter-plate space. The mid-plate may also comprise first andsecond valve stations, each defined by a valve diaphragm and the firstside of the mid-plate, the valve diaphragm seated against the first sideof the midplate and having an excursion range defined by the width ofthe first inter-plate space. There is a pump actuation channel for thepump station, and a valve actuation channel for each of the first andsecond valve stations. The pump actuation channel runs parallel to theface of the cassette in the first inter-plate space connecting a pumpactuation chamber bounded by the first plate and the pump diaphragm witha cassette pump actuation port located within the first inter-platespace at a first edge of the cassette. And each of the valve actuationchannels run parallel to the face of the cassette in the firstinter-plate space connecting a valve actuation chamber bounded by thefirst plate and the valve diaphragm with a cassette valve actuation portlocated within the first inter-plate space at the first edge of thecassette. There may be an inlet and outlet valve fluid port in each ofthe two valve stations, and one or more pump fluid ports in the pumpstation, each of the valve and pump fluid ports fluidly connecting afluid channel in the second inter-plate space with: a pumping chamberdefined by the pump diaphragm and the first side of the mid-plate, and avalve fluid chamber in each of said valve stations defined by thecorresponding valve diaphragm and the first side of the mid-plate. Thefluid channel has a flowpath that passes through the inlet and outletvalve fluid ports and the one or more pump fluid ports, so thatselective actuation of the pump actuation chamber and the valveactuation chambers allows for uni-directional flow of a fluid throughthe fluid channel. A fluid channel may run in the second inter-platespace, and fluidly connect to: a pumping chamber defined by the pumpdiaphragm and the first side of the mid-plate, the connection being madethrough a pump fluid port in the mid-plate, and a valve fluid chamber ofeach valve station, each of the valve fluid chambers being defined bythe corresponding valve diaphragm and the first side of the mid-plate,each of the connections being made through two valve fluid ports in themid-plate, so that the fluid channel runs parallel to the face of thecassette in the second inter-plate space connecting the pumping chamberand each of the valve fluid chambers with a cassette fluid inlet portand a cassette fluid outlet port located within the second inter-platespace at the first edge or at a second edge of the cassette. Thecassette fluid inlet port and cassette fluid outlet port may be locatedat a second edge of the cassette, so that the cassette pump actuationport and the cassette valve actuation port are configured to be pluggeddirectly into a mating actuation receptacle external to the cassette,and so that the fluid inlet port and fluid outlet port are arranged tobe connected via flexible or malleable tubing to a fluid source ordestination external to the cassette. A fluid channel may run in thesecond inter-plate space, and fluidly connect to: a pumping chamberdefined by the pump diaphragm and the first side of the mid-plate, theconnection being made through a pump fluid port in the mid-plate, and avalve fluid chamber of each valve station, each of the valve fluidchambers being defined by the corresponding valve diaphragm and thefirst side of the mid-plate, each of the connections being made throughtwo valve fluid ports in the mid-plate. The fluid channel may then runparallel to the face of the cassette in the second inter-plate space andconnect the pumping chamber and each of the valve fluid chambers with acassette fluid inlet port and a cassette fluid outlet port, the cassettefluid inlet port and fluid outlet port exiting the cassette throughrigid conduits originating on the mid-plate and penetrating the face ofthe cassette through the first or second outer plates.

In a further embodiment, a plurality of walls may be formed on the firstand second sides of the mid-plate, said walls arranged to be fused withthe first and second plates to form the actuation or fluid channelswithin the cassette. A first type of the walls may comprise parallelwalls to define the actuation or fluid channels, a second type of thewalls may comprise circumferential perimeter walls defining pump orvalve actuation stations, and a third type of the walls may compriseadjacent end walls defining a channel termination at which a valve orpump fluid port penetrates the mid-plate. The first plate may compriseone or more circumferential valve or pump diaphragm retainers configuredto fit within the circumferential perimeter walls of the opposingmid-plate that define pump or valve actuation stations, the retainersarranged to clamp a peripheral bead or rim of an associated diaphragmpositioned in the pump or valve station of the mid-plate. The retainersmay include holes, fenestrations or slots to permit transmission ofactuation fluid or gas between the valve or pump actuation chambersurrounded by the retainer and an associated actuation channel. Thefirst plate may comprise an elongate rib configured to be positionedwithin a mating actuation channel of the mid-plate, the cross-sectionalsize and length of the rib arranged to adjust the actuation channelvolume to a pre-determined value between an actuation port of thecassette and an associated valve or pump actuation chamber.

In another embodiment, a fluid handling cassette may comprise amid-plate positioned between a first plate and a second plate, saidplates having a length, a width and a plate thickness, a first side ofthe mid-plate opposing the first plate and a second side of the mid-pateopposing the second plate, The first plate is spaced apart from themid-plate defining a width of a first inter-plate space, and the secondplate is spaced apart from the mid-plate defining a width of a secondinter-plate space. An edge of the cassette has a cassette thicknessdefined by the thickness of each plate plus the width of the first andsecond inter-plate spaces, and a face of the cassette being defined bythe length and width of the first or second plate. The mid-plate maycomprise first and second valve stations, the first valve stationdefined by a first valve diaphragm and the first side of the mid-plate,and the second valve station defined by a second valve diaphragm and thesecond side of the mid-plate, the first valve diaphragm seated againstthe first side of the midplate and having an excursion range defined bythe width of the first inter-plate space, and the second valve diaphragmseated against the second side of the mid-plate and having an excursionrange defined by the width of the second inter-plate space. A firstvalve actuation channel for the first valve station may run parallel tothe face of the cassette in the first inter-plate space, and a secondvalve actuation channel for the second valve station may run parallel tothe face of the cassette in the second inter-plate space. The firstvalve actuation channel connects a first valve actuation chamber boundedby the first plate and the first valve diaphragm with a first cassettevalve actuation port located within the first inter-plate space at afirst edge of the cassette, and the second valve actuation channelconnects a second valve actuation chamber bounded by the second plateand the second valve diaphragm with a second cassette valve actuationport located within the second inter-plate space at the first edge ofthe cassette.

In another embodiment, a fluid handling cassette may comprise amid-plate positioned between a first plate and a second plate, theplates having a length, a width and a plate thickness, a first side ofthe mid-plate opposing the first plate and a second side of the mid-pateopposing the second plate. The first plate is spaced apart from themid-plate defining a width of a first inter-plate space, and the secondplate is spaced apart from the mid-plate defining a width of a secondinter-plate space. An edge of the cassette has a cassette thicknessdefined by the thickness of each plate plus the width of the first andsecond inter-plate spaces, and a face of the cassette being defined bythe length and width of the first or second plate. The mid-plate maycomprise first and second pump stations, the first pump station definedby a first pump diaphragm and the first side of the mid-plate, and thesecond pump station defined by a second pump diaphragm and the secondside of the mid-plate, the first pump diaphragm seated against the firstside of the midplate and having an excursion range defined by the widthof the first inter-plate space, and the second pump diaphragm seatedagainst the second side of the mid-plate and having an excursion rangedefined by the width of the second inter-plate space. A first pumpactuation channel for the first pump station may run parallel to theface of the cassette in the first inter-plate space, and a second pumpactuation channel for the second pump station may run parallel to theface of the cassette in the second inter-plate space, the first pumpactuation channel connecting a first pump actuation chamber bounded bythe first plate and the first pump diaphragm with a first cassette pumpactuation port located within the first inter-plate space at a firstedge of the cassette. The second pump actuation channel connects asecond pump actuation chamber bounded by the second plate and the secondpump diaphragm with a second cassette pump actuation port located withinthe second inter-plate space at the first edge of the cassette.

In another embodiment, a fluid-handling cassette assembly may comprise amiddle cassette interposed between a first outer cassette and a secondouter cassette, each cassette comprising: a mid-plate positioned betweena first plate and a second plate, the plates having a length, a widthand a plate thickness, a first side of the mid-plate opposing the firstplate and a second side of the mid-pate opposing the second plate. Thefirst plate is spaced apart from the mid-plate defining a width of afirst inter-plate space, and the second plate is spaced apart from themid-plate defining a width of a second inter-plate space. An edge of thecassette has a cassette thickness defined by the thickness of each plateplus the width of the first and second inter-plate spaces, and a face ofthe cassette is defined by the length and width of the first or secondplate. A plurality of diaphragm valves or pumps comprising valve or pumpactuation chambers may be connected to actuation channels runningparallel to the face of the cassette within the first or secondinter-plate space, and terminating in respective cassette valve or pumpactuation ports at a first edge of the cassette between the first orsecond inter-plate space. A fluid-handling pod is positioned in aninter-cassette space between the middle cassette and the first or secondcassette, the pod having a fluid connection to fluid channels in themiddle, first or second cassette via a fluid conduit penetrating theface of the middle, first or second cassette. The first edge of themiddle, first and second cassettes are located on a first side of thecassette assembly, so that the cassette valve or pump actuation portsare configured to plug into or unplug from an actuation port receptacleassembly opposite the first side of the cassette assembly. Thefluid-handling pod may comprise a diaphragm pump pod having an actuationand a fluid connection to actuation and fluid channels in the middle,first or second cassette via an actuation conduit and a fluid conduit,each penetrating the face of the middle, first or second cassette. Theactuation conduit of the diaphragm pump pod may connect to an actuationchannel in a first or second inter-plate space of the middle, first orsecond cassette, and has an uninterrupted connection to a cassetteactuation port for the diaphragm pump pod on the first edge of themiddle, first or second cassette. The fluid conduit of the diaphragmpump pod may connect to a fluid channel in a first or second inter-platespace of the middle, first or second cassette, and may connect with adiaphragm valve in the cassette, and an actuation channel of thediaphragm valve may connect to a cassette actuation port for thediaphragm valve in the first edge of the middle, first or secondcassette. The fluid conduit in any of these arrangements may be rigid. Aplurality of fluid-handling pods may be positioned between the middlecassette and the first cassette, and between the middle cassette and thesecond cassette, and the associated fluid conduits of this plurality offluid-handling pods may be rigid to provide structural support for thecassette assembly. A cassette assembly frame may be configured toenhance the structural stiffness of the cassette assembly, the cassetteassembly frame comprising a rigid support plate on a second side of thecassette assembly opposite the first side of the cassette assembly, thesupport plate configured to engage a cassette loading apparatus oppositethe actuation port receptacle.

In another embodiment, a fluid-handling cassette assembly may comprise:a middle cassette interposed between a first outer cassette and a secondouter cassette, each cassette comprising a mid-plate positioned betweena first plate and a second plate, the plates having a length, a widthand a plate thickness, a first side of the mid-plate opposing the firstplate and a second side of the mid-pate opposing the second plate. Thefirst plate is spaced apart from the mid-plate defining a width of afirst inter-plate space, and the second plate is spaced apart from themid-plate defining a width of a second inter-plate space. An edge of thecassette has a cassette thickness defined by the thickness of each plateplus the width of the first and second inter-plate spaces, and a face ofthe cassette being defined by the length and width of the first orsecond plate. A plurality of diaphragm valves or pumps may comprisevalve or pump actuation chambers connected to actuation channels runningparallel to the face of the cassette within the first or secondinter-plate space, and terminating in respective cassette valve or pumpactuation ports at a first edge of the cassette between the first orsecond inter-plate space. A first fluid-handling pod may be positionedin an inter-cassette space between the middle cassette and the first orsecond cassette; the fluid-handling pod having a fluid connection tofluid channels in the middle, first or second cassette via a fluidconduit penetrating the face of the middle, first or second cassette. Asecond fluid-handling pod may comprise a diaphragm pump pod having anactuation and a fluid connection to actuation and fluid channels in themiddle, first or second cassette via an actuation conduit and a fluidconduit, each penetrating the face of the middle, first or secondcassette. The first edge of the middle, first and second cassettes maythen located on a first side of the cassette assembly, so that thecassette valve or pump actuation ports are configured to plug into orunplug from an actuation port receptacle assembly opposite the firstside of the cassette assembly. The actuation conduit of the diaphragmpump pod may connect to an actuation channel in a first or secondinter-plate space of said middle, first or second cassette, and may havean uninterrupted connection to a cassette actuation port for thediaphragm pump pod on the first edge of said middle, first or secondcassette. The fluid conduit of the diaphragm pump pod may connect to afluid channel in a first or second inter-plate space of the middle,first or second cassette, and may connect with a diaphragm valve in thecassette, and an actuation channel of the diaphragm valve may thenconnect to a cassette actuation port for the diaphragm valve in thefirst edge of said middle, first or second cassette. The fluid conduitmay be rigid. There may be a plurality of fluid-handling pods betweenthe middle cassette and the first cassette, and between the middlecassette and the second cassette, and associated fluid conduits of thisplurality of fluid-handling pods may be rigid, providing structuralsupport for the cassette assembly. A cassette assembly frame may beconfigured to enhance the structural stiffness of the cassette assembly,the cassette assembly frame comprising a rigid support plate on a secondside of the cassette assembly opposite the first side of the cassetteassembly, the support plate configured to engage a cassette loadingapparatus opposite the actuation port receptacle.

In another aspect of the invention, a manifold adaptor is configured toconnect a pressure distribution manifold with a liquid-handling cassetteassembly. A housing has a first side comprising a first set of transferports configured to connect to actuation output ports of the manifold,and has an opposing second side comprising a second set of transferports configured to connect to actuation input ports of the cassetteassembly. The first set of transfer ports comprises a first spatialarray configured to match a spatial array of the actuation output portsof the manifold. The second set of transfer ports comprises a secondspatial array configured to match a spatial array of the actuation inputports of the cassette assembly, and the first spatial array of transferports is different from the second spatial array of transfer ports. Thefirst spatial array may cover an area of the first side of the adaptorhousing having a first length and a first width, and the second spatialarray covers an area of the second side of the adaptor housing having asecond length and a second width; and the second length may be greaterthan the first length, so that the housing of the manifold adaptoroverhangs a side of the manifold. The second side of the housing mayinclude an elastomeric wiper gasket comprising a plurality of wiperseals, each of the plurality of wiper seals being associated with atransfer port on the second side of the adaptor housing. The wipergasket can be embedded under a top plate of the adaptor housing.

In another aspect, a seating apparatus is described for a cassettehaving a plug-in side and an opposing mounting side. The seatingapparatus comprises: a stationary frame member connected to a movablecassette mount by a plurality of linkages on a first side of thecassette mount and on an opposing second side of the cassette mount. Thelinkages on the first side of the cassette mount are connected to afirst stationary flange of the stationary frame member, and the linkageson the second side of the cassette mount connected to a secondstationary flange of the stationary frame member. The linkages each maycomprise a swing-arm having a first end pivotally coupled to thestationary flange and a second end coupled to an elongate slot in thecassette mount. The second end of the swing-arm can be configured tomove in an arcuate path to move the cassette mount, so that the elongateslot restricts movement of the cassette mount by the swing arm to alinear motion toward or away from the stationary frame member. Thecassette mount may comprise a first moveable flange and a first rail atthe first side of the cassette mount, and a second moveable flange and asecond rail at the second side of the cassette mount. Each of themoveable flanges may have a surface generally parallel to the directionof movement of the cassette mount, the elongate slot being formed in themoveable flange and oriented perpendicular to the direction of movementof the cassette mount, and the first and second rails may then beconfigured to hold the mounting side of the cassette. A handle assemblymay be pivotally connected to the cassette mount, so that movement of ahandle of the handle assembly in a direction away from the stationaryframe member moves the cassette mount away from the stationary framemember; and movement of the handle in a direction toward the stationaryframe member moves the cassette mount toward the stationary framemember. The pivotal connection of the handle assembly may comprise afirst pivotal connection of a first handle arm to the first stationaryflange, a second pivotal connection of a second handle arm to the secondstationary flange, a third pivotal connection of the first handle arm toa handle swing arm connected to the first moveable flange of thecassette mount, and a fourth pivotal connection of the second handle armto a handle swing arm connected to the second moveable flange of thecassette mount. The first and third pivotal connections and the secondand fourth pivotal connections may be spaced apart from each other onthe first and second handle arms. A third stationary flange of thestationary frame member may face the handle assembly and may begenerally perpendicular to the first and second stationary flanges. Thehandle assembly may include a spring-loaded plunger configured to engagea hole or recess in the third stationary flange, so that the cassettemount may be locked into a retracted position when the handle of thehandle assembly is moved toward the stationary frame member.

BRIEF DESCRIPTION OF THE DRAWINGS

Non-limiting embodiments of the present invention will be described byway of example with reference to the accompanying figures, some of whichare schematic, and are not intended to be drawn to scale. In thefigures, each identical or nearly identical component illustrated istypically represented by a single numeral. For purposes of clarity, notevery component is labeled in every figure, nor is every component ofeach embodiment of the invention shown where illustration is notnecessary to allow those of ordinary skill in the art to understand theinvention.

FIGS. 1A-1B are schematic cross section views of an embodiment of a pumpcassette during a fill stroke and a deliver stroke;

FIGS. 2A-2B are schematic cross-section views of another embodiment of apump cassette during a fill stroke and a deliver stroke;

FIGS. 3A-3B are schematic cross-section views of an exemplary diaphragmvalve during operation;

FIGS. 4A-4B are schematic cross-section views of another embodiment of apump cassette during operation;

FIGS. 5A-5B are schematic cross-section views of optional additionalfeatures of exemplary pump cassettes during operation;

FIG. 6 is a perspective view of an exemplary pump or valve cassette;

FIG. 7 is a front perspective view of the pump or valve cassette shownin FIG. 6;

FIG. 8 is a perspective view of an inner side of an outer plate of theexemplary cassette shown in FIGS. 6 and 7;

FIG. 9 is a perspective view of an actuation side of a midplate of theexemplary cassette shown in FIGS. 6, 7 and 8;

FIG. 10 is a close-up view of pump and valve stations of the actuationside of the midplate shown in FIG. 9.

FIG. 11 is a perspective view of a fluid side of a midplate of anexemplary pump or valve cassette;

FIG. 12 is a perspective view of another embodiment of a pump or valvecassette;

FIG. 13 is a perspective view of a first side of a midplate of theexemplary cassette shown in FIG. 12;

FIG. 14 is a perspective view of a second side of the midplate shown inFIG. 13;

FIG. 15 is a rear perspective view of a cassette assembly;

FIG. 16 is a front perspective view of the cassette assembly shown inFIG. 15;

FIGS. 17A-17B depict front and rear perspective views of anotherembodiment of a cassette assembly;

FIG. 18 is an exploded view of a prior exemplary cassette assembly;

FIG. 19 is a side view of an assembled cassette assembly of FIG. 18,showing the pneumatic actuation lines of the assembly and associatedconnectors;

FIG. 20 is a perspective view of another embodiment of a cassetteassembly secured in a frame assembly;

FIG. 21 is an exploded view of the frame assembly shown in FIG. 20;

FIGS. 22A-22B are front and rear perspective views of a top plate of theexemplary frame assembly;

FIG. 23 is a front perspective view of a hemodialysis apparatus;

FIG. 24 is a front perspective view of a housing of the hemodialysisapparatus shown in FIG. 23;

FIG. 25 is a rear perspective view of the housing shown in FIG. 24;

FIGS. 26-29 are schematic representations of an exemplary pressuredistribution manifold;

FIG. 30 is a perspective view of an upper portion of the housing of FIG.24, enclosing a cassette assembly that is disconnected from acorresponding manifold assembly;

FIG. 31 is a perspective view of the upper portion of the housing asshown in FIG. 30, with the cassette assembly connected to thecorresponding manifold assembly;

FIG. 32 is a rear perspective view of an exemplary pressure distributionmanifold and associated interfacing adaptors;

FIG. 33 is an exploded view of the pressure distribution manifold shownin FIG. 32;

FIG. 34 is a perspective view of the exemplary pressure distributionmanifold and an associated sensor board;

FIG. 35 is a perspective view of a lower block of the pressuredistribution manifold shown in FIG. 34;

FIGS. 36-37 are inferior and superior perspective views of an upperblock of the pressure distribution manifold shown in FIG. 34;

FIG. 38 is a flowpath schematic of an arrangement of pneumatic channelsin the exemplary pressure distribution manifold;

FIG. 39 is a perspective view of an exemplary pneumatic channel in thepressure distribution manifold;

FIG. 40 is a perspective view of the disposition of the exemplarypneumatic channel shown in FIG. 39 in the pressure distributionmanifold;

FIG. 41 is a flowpath schematic of an arrangement of pneumatic channelsin the exemplary pressure distribution manifold;

FIG. 42 is a perspective view of another exemplary pneumatic channel inthe pressure distribution manifold;

FIG. 43 is a perspective view of the disposition of the exemplarypneumatic channel shown in FIG. 42 in the pressure distributionmanifold;

FIG. 44 is a rear perspective view of a hemodialysis device housing,showing the placement of the pressure distribution manifold;

FIG. 45 is a front perspective view of the hemodialysis device housing,showing installation of the exemplary manifold adaptors;

FIG. 46 is a front-left side perspective view of the exemplary cassetteassembly positioned in an upper portion of the housing, and aligned withthe manifold adaptors;

FIG. 47 is a perspective view of the exemplary pneumatic distributionmanifold, positioned below the housing cutouts for the manifoldadaptors;

FIG. 48 is a rear perspective view of the hemodialysis device housing,showing installation of the exemplary pressure distribution device andthe interfacing adaptors;

FIG. 49 is a front perspective view of the hemodialysis device housing,showing installation of the exemplary interfacing adaptors;

FIG. 50 is a partial cutaway view of the hemodialysis device housing,showing an exemplary cassette loading assembly mounted on the ceiling ofthe housing;

FIG. 51 is a perspective view of an exemplary manifold adaptor rail;

FIG. 52 is a partially exploded superior perspective view of anexemplary manifold adaptor positioned over the pressure distributionmanifold;

FIG. 53 shows the partially exploded view of the manifold adaptor ofFIG. 52, viewed from an inferior perspective;

FIG. 54 is a plan view of an exemplary wiper gasket of a manifoldadaptor;

FIG. 55 is a cross-sectional view of a section of the wiper gasket ofFIG. 54;

FIG. 56 is an inferior perspective view of the exemplary cassetteloading assembly when the operating handle is in a raised (disengaged)configuration;

FIG. 57 is a front perspective view of the exemplary cassette loadingassembly when the operating handle is in a lowered (engaged)configuration;

FIG. 58 is an inferior perspective view of the exemplary cassetteloading assembly of FIG. 57 with the operating handle in a loweredconfiguration;

FIG. 59 is a rear perspective view of the exemplary cassette loadingassembly of FIGS. 57 and 58 with the operating handle in a loweredconfiguration;

FIG. 60 is a schematic representation of a fluid flowpath in thehemodialysis device;

FIGS. 61 and 62 are graphical representations of pressure variation inan actuation chamber of a pump in the hemodialysis device;

FIG. 63 is an exemplary flowchart for an algorithm to control pressureof an actuation chamber of a pneumatically actuated pump;

FIG. 64 is an exemplary flowchart for an alternative pressure controlalgorithm for a pneumatically actuated pump;

FIG. 65 is an exemplary flowchart for an end-of-stroke detectionalgorithm for an exemplary pneumatically actuated pump;

FIG. 66 is an exemplary flowchart for an occlusion detection algorithmfor fluid pathways in a diaphragm-based pumping system;

FIG. 67 is an exemplary flowchart for an algorithm to determineresistance to flow during a pumping fill stroke;

FIG. 68 is a schematic representation of the fluid flowpaths in anexemplary hemodialysis system;

FIG. 69 is a schematic representation of an isolated view of a sectionof the fluid flowpaths of the hemodialysis system shown in FIG. 68;

FIG. 70 is a state diagram representing a disinfect procedure for thehemodialysis system; and

FIG. 71 is a state diagram representing temperature control prior to andduring a disinfect procedure.

DETAILED DESCRIPTION

Cassettes with Liquid and Pneumatic Channels in Plane

In some pumping applications, it is advantageous to position theactuation ports of a fluidically or pneumatically actuated pump or valvecassette on the edge, thin or narrow side of the cassette, rather thanon the broad side of the cassette. This allows the cassette to beplugged thin-side rather than broad-side into a receptacle comprising anarray of actuation ports associated with a pressure delivery manifold.This may allow one to maximize the functions a pump/valve cassette canperform within a confined space. In some circumstances, overall spaceconstraints may also make it advantageous to minimize the totalthickness of the cassette. This can be achieved by making the cassetteonly minimally thicker than the excursion range of enclosed diaphragms.Ideally, each outer plate of the cassette functions primarily as theroof or end wall of any pump or valve actuation or liquid carryingchamber or channel, with a thickness insufficient to fully enclose anyliquid or actuation channels to run generally parallel to the face orbroad side of the cassette. The actuation channels are configured to runin a space between a midplate and an outer plate (e.g. first outerplate) of the cassette, within an inter-plate space that defines themaximum excursion range of one or more diaphragms of the cassette. Thewidth of the inter-plate space (and consequently the maximum excursionrange of a flexible membrane or diaphragm) can be pre-determined by theheight of channel walls formed on the actuation and/or liquid-carryingside of the cassette midplate. The height of the channel walls on oneside of a midplate may be different from the height of the channel wallson the opposing side of the midplate. For example, to accommodate adesired fluid flow rate, the channels walls on a liquid side of themidplate may be higher to provide for a greater cross-sectional area ofthe liquid-carrying channels, whereas the cross-sectional requirements(and thus the channel wall height) of the actuation channels on theactuation side of the midplate may be smaller.

FIGS. 1A and 1B illustrate schematically a cassette 10 in cross-sectionnear the end of a fill stroke, and near the end of a deliver stroke,respectively. A midplate 12 is positioned between a first outer plate 14and a second outer plate 16. A flexible diaphragm 18 is positioned inthe first inter-plate space 20, and liquid flow channels are present inthe second inter-plate space 22. To reduce the thickness of a pumpand/or valve cassette, any actuation channels preferably run in thefirst inter-plate space 20, a space defined by the excursion depth,depth of travel or linear range E that a diaphragm travels between themidplate 12 and the first outer plate 14. In the case of an onboarddiaphragm pump, its stroke volume is a function of the depth ofexcursion E of its diaphragm 18 and the effective surface area thediaphragm occupies on the broad side of the cassette. The preferreddepth of excursion E of a diaphragm may also depend on how efficientlythe stroke volume of the diaphragm can be increased by increasing itseffective surface area. In this embodiment, two pump chamber liquidports 24 a, 24 b are shown, representing an inlet and an outlet, eachconnected to separate fluid channels within inter-plate space 22, thefluid channels schematically separated by wall 38. (The direction ofliquid flow shown is arbitrary, and depends on which liquid line is openor closed by a downstream valve during a diaphragm fill stroke ordelivery stroke). In another embodiment, as shown in FIGS. 2A and 2B, asingle pump chamber liquid port 24 c (or two or more such ports) may beused, which then alternates between being an inlet port and an outletport depending on which downstream valves are open or closed in thesingle liquid line in inter-plate space 22. When the volume of actuationchamber 26 is at a minimum, the corresponding pump chamber 28 is at amaximum (fill stroke, see FIG. 1A, 2A). When the volume of actuationchamber 26 is at a maximum, the volume of corresponding pump chamber 28is at a minimum (deliver stroke, see FIG. 1B, 2B). Once the excursiondepth E of the diaphragms on the cassette have been chosen, the cassettethickness T can be reduced by avoiding locating actuation ports directlyover the diaphragms being actuated (as in prior art designs). This isaccomplished by placing the actuation ports on the thin or narrow sideof the cassette and running actuation channels to their respectivediaphragms in the first inter-plate space 20 in the cassette 10. Thisspace is delimited by midplate 12 onto which the diaphragm 18 is seatedand first outer plate 14 that provides a cover or roof for the actuationchamber 26 for each diaphragm 18. Surrounding the perimeter of eachdiaphragm is a wall 30 spanning the inter-plate space 20 that, togetherwith the outer plate 14, completes each actuation chamber 26, except foran actuation port or window 32 connecting the actuation chamber 26 toits corresponding actuation channel (represented by the arrow in thefirst inter-plate space 20). The actuation channel then runs in theinter-plate space 20 to a peripheral edge or narrow side of thecassette, terminating there as a cassette actuation port (see, e.g. FIG.9). Note that the actuation channel can be smaller than the depthprovided by the inter-plate space 20, depending on what excursion depthE has been specified for the diaphragm 18. To minimize the overallthickness T of the cassette 10 for a given specified diaphragm excursiondepth E, one can minimize the nominal thickness P of each plate 12, 14,16 (within structural rigidity constraints, and any constraints placedon achieving a proper welding or cementing of the outer plate to thechannel walls of the midplate). Depending on fluid flow raterequirements, one can also minimize the thickness of the cassette byreducing the depths of the liquid flow channels (i.e. the height of thechannel walls) within the second inter-plate space 22.

The overall thickness T of the cassette can depend on the amount ofdepth required by the liquid flowpaths or channels on an opposing sideof the midplate 12 of the cassette 10 within the second inter-platespace 22. In the pump shown in FIGS. 1A-1D and the valve shown in FIGS.3A, 3B, the required depth of the liquid channel determines the depth ofthe second inter-plate space 22. Depending on the liquid flow ratesspecified for the cassette, the second inter-plate space 22 may have adepth L substantially smaller than the depth E of the first inter-platespace 20. As shown in FIGS. 3A,B, for any given diaphragm valve station,there are at least two liquid channels: a first channel terminating intovalve port 34 a of midplate 12, and a second channel terminating intovalve port 34 b of midplate 12. (In some embodiments a plurality ofliquid channels could terminate into separate valve ports in themidplate of a single valve station). As shown in FIGS. 3A and 3B, theexcursion depth E is determined in the case of a diaphragm valve by thedegree of relaxation required to allow the diaphragm 18 to lift awayfrom the fluid ports 34 a,b it is designed to occlude. The valvediaphragm 36 may then move away from the ports 34 a, b under negativeactuation pressure to allow liquid flow as shown in FIG. 3A, or may moveto occlude the ports 34 a, b under positive actuation pressure tointerrupt liquid flow as shown in FIG. 2B. The separate liquid channelsin the valve station of a cassette are represented schematically by thewall 38 shown in the second inter-plate space 12. In the illustrationshown, the valve ports 34 a, b may optionally comprise raised elements40 (placed circumferentially around the valve port) to improve thesealing efficiency of the diaphragm. Such a raised element may only needbe present around one of the valve ports to be effective. Thus as thevalve diaphragm relaxes or is drawn away from the liquid ports of thevalve, liquid is allowed to flow from one liquid channel, through itsassociated port into a liquid valve chamber, and then out through theliquid port of a second liquid channel connected to that valve station.The choice of cross-sectional area of the liquid channels may depend ona desired liquid flow resistance and a desired hold-up volume or deadspace occupied by the liquid channels in the cassette. The desiredcross-sectional area of the liquid channels will in turn determine thedepth of the liquid channel (or channel wall height) occupying thesecond inter-plate space 22 between the cassette midplate 12 and thesecond outer plate 16. The liquid and actuation channels may be formedfrom the midplate or the respective outer plates, or may be formedindependently of the outer plates or midplate. In a preferredarrangement, the midplate is formed in a mold, 3-D printed or otherwisecast with the desired channel walls on both sides of the midplate, sothat the construction of the outer plates can be simplified. The outerplate 14 may comprise the roof or diaphragm-limiting wall of theactuation chamber 26, and the outer plate 16 may comprise the roof orthe liquid channels in the cassette. In this way, the inter-plate spacebetween the midplate and the outer plates can be further reduced.

As shown in FIG. 1A, in a preferred embodiment the thickness T of a pumpor valve cassette 10 can thus be defined by the nominal thicknesses P ofeach of the midplate and the two outer plates, plus the excursion depthE of the diaphragm 18 and the depth L of the liquid channels defined bythe second inter-plate space 22 provided on the cassette. To maximizethe efficiency of positioning and distributing valve and pump stationson the midplate 12, it may be advantageous to place some actuationchannels and actuation chambers on both opposing sides of a singlemidplate 12. In this case, the thickness T of a cassette will bedetermined by the excursion depth of the largest diaphragm on each sideof the midplate. For example, if the excursion depths E of the pumpdiaphragms are the same on each side of the midplate 12, then thethickness T of the cassette will be equal to (2×E)+(3×P).

FIGS. 4A and 4B show an alternate embodiment of a diaphragm pump of apump cassette 50. In this case, the pump chamber fluid ports have beenreplaced by a wide aperture 42 through which diaphragm 44 can pass as itmoves from a fill position (FIG. 4A) to a deliver position (FIG. 4B).The overall thickness T′ of this cassette is thus determined from thetotal excursion distance or length E′ of the diaphragm 44, plus thethickness P of the two outer plates 46, 48. The pump diaphragm 44exploits virtually the entire thickness of the cassette 50 tosubstantially increase the stroke volume of the pump. In this case, thepumping chamber 52 is defined by the liquid side of diaphragm 44 and acircumferential sealing wall 54 capped by the second outer plate 48.Liquid inlet/outlet pump ports 56, 58 are shown in this embodiment,although other embodiments may include only a single port acting as bothinlet and outlet, or may include a plurality of ports whose inlet oroutlet function is determined by downstream valves in liquid channelsassociated with each pump port. In this arrangement, the overallthickness of a cassette can be minimized, because the stroke volumegenerated by the diaphragm is essentially doubled in the absence of themidplate. For any desired pump stroke volume, the inter-plate distancescan thereby be reduced substantially.

FIGS. 5A and 5B show additional features that optionally may be includedin a pump or valve cassette. In this case diaphragms 60, 62 are shown tobe secured against the midplate 12 by a diaphragm retainer or retainingwall 68 (also see retainer 100 in FIG. 8). In other embodiments, theperimeter bead 64, 66 respectively of diaphragms 60, 62 can be securedto the midplate 12 by an adhesive, by heat welding, by having a sectionof the midplate over-molded to surround and clamp the bead, by applyinga solid continuous ring into position against the diaphragm bead, or bya number of other methods that ensure that the diaphragm is secured tothe midplate and that a seal is formed between the diaphragm bead andmidplate to segregate the liquid chamber 28 from the actuation chamber26. In the example shown, a retainer or retaining wall 68, 100 isinstalled inside the perimeter wall 30 of the actuation chamber 26.Shown in cross-section, the illustrated portion of the retaining wall 68displays two fenestrations, slots, windows or holes 70 that permitactuation pressure (e.g. pneumatic pressure) to be transmitted to theactuation side of the diaphragm 60. For most of its circumference, theretainer or retaining wall 68 extends uninterrupted from the inner sideof the first outer plate 14 or 46 to a position adjacent the bead 64, 66of diaphragm 60, 62. If the bead is made of elastomeric material, theretainer or retaining wall 68, 100 acts to partially compress the beadduring assembly of the cassette as the first outer plate is installedagainst the opposing mid-plate. A tight fit helps to ensure that thediaphragm is securely installed and that an air/water-tight seal hasbeen formed. In a preferred arrangement, two or even a plurality ofretaining wall fenestrations 70 (or holes) can be distributed around thecircumference of the retaining wall 68, so that positive or negativeactuation pressure can be transmitted to a plurality of sections of thediaphragm 60, 62 relatively simultaneously.

In some cases, it may be advantageous to ensure that there is acontinuous rigid clamping structure against the entire circumference ofthe diaphragm bead or rim. In that case, a plurality of holes in theretention wall 68, 100 may be preferable to a slot that extends to thediaphragm bead. Alternatively, a continuous rigid ring (e.g. metal orplastic washer) (not shown) applied against the diaphragm bead can becombined with a slotted retention wall 68, 100 to achieve the sameresult. Preferably, the outer edge of the ring or washer abuts the innerside of the perimeter wall of the valve or pump station and compressesonly the bead portion of the diaphragm, and the inner edge of the ringor washer avoids contact with the diaphragm as it transitions from thediaphragm bead to the diaphragm body.

In the example shown, the diameter of the retainer or retaining wall 68,100 is small enough to allow a gap 72 to exist between it and theperimeter wall 30 of the actuation chamber 26. The gap 72 permitsfluidic or pneumatic actuation pressure to be distributed to theindividual fenestrations 70 of the retaining wall 68. The retainer orretaining wall 68, 100 can be a separate element that is assembled withthe other components of the cassette, or it may be formed or co-moldedwith either the midplate 12 or the first outer plate 14 of the cassette.

FIGS. 5A and 5B also illustrate that the inner wall of the actuation orfirst outer plate 14 or 46 optionally can comprise a curved buttress 74or 76 that helps to conform the inner wall of the actuation chamber 26to the curvature of the diaphragm 60, 62 as it extends fully toward theactuation-side first plate 14 or 46. This may help to reduce stress onthe more peripheral portions of the diaphragm 60, 62 when fullyretracted into the actuation chamber 26. Similarly, as shown in FIG. 5B,a curved buttress 78 can be positioned along the end wall (liquid orsecond outer plate 48) of the liquid pumping chamber 52 for a similarreason. In these examples, shaping the inner wall of the outer plates14, 46 and 48 does not require the overall thickness of either cassette10 or 50 to be increased. The buttresses 74, 76, 78 can either beseparate inserts attached to the respective outer plates, or may beformed and co-molded with the outer plates such that any additionalthickness of the outer plate is made to encroach the inter-plate spacerather than extending beyond the outer surface of the outer plate. Theouter plates may be molded to curve inward from the outside of the platetoward the actuation chamber or liquid chamber, while not increasing theoverall thickness of the cassette.

FIG. 6 shows a rear perspective view of an exemplary cassette 80 thatincludes a plurality of valve stations 82 and an exemplary pump station84. In one example, a cassette was constructed to have a length of about16 cms, a width of about 19 cms and a thickness of about 1.5 cms. Thefirst outer plate or actuation plate 86 has been molded withindentations on its external surface at the valve 82 and pump 84stations to provide a curved inner surface to conform with theassociated diaphragms in those regions. In this example, the nominalthickness of each of the first outer plate 86, the second outer plate orliquid-side plate 88 and the midplate 90 is approximately 2 mm, whereasthe overall thickness of the cassette is approximately 15 mm. The first92 and second 94 inter-plate spaces are each approximately 4.5 mm wide.In this example, the pump diaphragm has an excursion range approximatelyequal to the 4.5 mm wide first inter-plate space 92. The cassetteactuation channel ports 96 are shown arrayed within the firstinter-plate space 92 of the cassette 80. Thus a diaphragm excursion ofabout 4.5 mm can be achieved in a cassette whose width is about 10.5 mmplus the width desired for liquid channels in the second inter-platespace 94. In this case the second inter-plate space 94 has the samewidth as the first inter-plate space 92, but in other embodiments itcould be less (depending on the flow characteristics desired for theliquid channels). In this example, the excursion range of a cassettediaphragm is about 30% of the total cassette width. FIG. 7 shows a frontperspective view of the cassette of FIG. 6, revealing the cassetteliquid channel ports 98 arrayed within the second inter-plate space 94of the cassette 80.

FIG. 8 shows a perspective view of the inner side of the first outerplate 86 of cassette 80. In this example, the diaphragm retainer orretaining walls 100, 102 have been molded as an integral part of theinternal side of the first outer plate 86. (In dual-duty cassettes, bothsides of the mid-plate may be pump or valve actuation sides, so thatboth the first and second outer plates may include retainers orretaining walls 100, 102). In this example, each diaphragm retainer 100,102 has a number of fenestrations or holes 104 and optionally a top-sidegroove 106 to distribute actuation pressure evenly over the diaphragm tobe retained against the midplate 90. The curved inner walls 108 of theouter plate 86 in the valve and pump stations are arranged to conformwith the associated diaphragm shape as it extends fully into theactuation chamber (within which the retainers 102 are placed). In somecases, optionally, ribs 109 may be included in the mold of the outerplate 86, which are configured to encroach mating actuation channels ofthe opposing midplate. Ribs 109 may be constructed to have across-sectional size and length to adjust the total volume of theassociated actuation channel to a pre-determined volume. (This may helpto minimize the amount of pneumatic gas volume to be delivered (orcompressed), and may improve the responsiveness of the associateddiaphragms to actuation by a pressure delivery manifold.

Actuation volume adjustment ribs may be particularly advantageous in anarrangement in which both sides of the midplate carry actuation and/orfluid channels, or in which the inter-plate space must accommodate agreater diaphragm excursion range. In that case, installing actuationvolume adjustment ribs reduces the transmission volume of the actuationchannels and may improve the performance of a cassette. In addition,when synchronous valve actuation is desired, it may be advantageous tomatch the actuation channel transmission volume between sets of valveshaving varying distances from the actuation ports of the cassette.Properly sized volume adjustment ribs can be used to fine-tune thecassette valve operations in this manner.

FIG. 9 shows a perspective view of the actuation side of the midplate 90of cassette 80. In this example, the actuation channels 110, valve andpump station perimeter walls 112, and cassette actuation ports 96 havebeen formed or molded as part of the midplate 90. In this example, mostof the diaphragm valve or pump stations are fed by a separate actuationchannel 110 leading from a dedicated cassette actuation port 96. Thecassette's fluidic or actuation channels can be a individually formedconduits, or each channel may comprise two walls spanning theinter-plate space, fused to and extending between the mid-plate andeither the first outer plate or the second outer plate. In some cases,it may be desirable to actuate two or more valve stations at once, inwhich case a single actuation channel path 114 can supply the two ormore valve stations, as shown with valve stations 116, 118. Each valvestation is surrounded by a perimeter wall 112 that seals the stationwhen the adjacent first outer plate 86 is welded to the midplate 90.

The cassette plates can be formed (e.g., injection molded) from moldableplastic material such as polysulfone that cures to a hard or rigidconsistency. Other plastics or materials such as metal can also be used.Other methods of molding can be used, as well as newer techniques suchas 3-D printing, to form the midplate and outer plates. The outer platescan be fused to the midplate using adhesives, or localized heating fromultrasonic or mechanical vibration. In a preferred method, the outerplates can be transparent, translucent, or can permit transmission oflaser wavelengths to allow laser welding of the outer plates to anopaque midplate. The welding seals the valve and pump regions of theouter plate to the perimeter walls and channels of the respective valveand pump stations of the midplate.

Each perimeter wall 112 forms part of the actuation chamber of therespective valve or pump station, and each communicates with anactuation channel 110 via an actuation chamber port 120 in the perimeterwall 112. The pump station 84 in this example has two pump ports 24 a,24 b connecting the liquid channel on the opposite (second) side of themidplate with the first side of the midplate shown in the drawing. Oneof these can function as a pump chamber inlet, while the other functionsas a pump chamber outlet. In other embodiments, the pump region can havea single pump port or a plurality of pump ports. The valve stations inthis example each have two ports connecting two separate liquid channelson the second side of the midplate with the valve station on the firstside of the midplate shown. Also, in this example, one of the valveports 34 a has a raised perimeter lip 40 to improve sealing of the valvediaphragm against the valve port when positive pressure is applied tothe diaphragm.

FIG. 10 shows a close-up view of the midplate 90 of FIG. 9. In thiscase, a pump diaphragm 122 and valve diaphragm 124 are shown to beinstalled in their respective pump and valve stations. The diaphragmsare held in place and sealed against the midplate 90 by correspondingretention walls or retainers 100, 102 shown in FIG. 8. Note that theretention walls or retainers 100, 102 fit (loosely) within thecircumference of the perimeter or chamber walls 112 of the respectivevalve or pump stations. The difference in diameter of the perimeter walland retention wall is sufficient to allow a gap 72 (see FIG. 5A) toexist between the two, so that actuation fluid or gas pressure can bedistributed uniformly around the associated diaphragm.

FIG. 11 shows the second side of midplate 90 of cassette 80. In thisexample, the liquid channels 126 have been molded in as part of themidplate 90. In the case of a pump station 84, each of the two ports 24a, 24 b is associated with a separate liquid channel 128, 130, so thatone port functions as an inlet port of the pump chamber, whereas theother port functions as an outlet port of the pump chamber. Whether aparticular port functions as an inlet or outlet can be determined bywhich downstream valve is actuated or closed.

FIG. 12 shows a variation of a cassette 132 that includes additionaloptional features (which may be individually included or excluded in anycassette design). In this case, the cassette incorporates actuationports, actuation channels and actuation chambers on both sides of amidplate 134. Each of the first inter-plate space 136 and secondinter-plate space 138 includes both actuation and liquid channels, aswell as actuation and liquid cassette ports. In this view, two rows ofactuation ports 140, 142 are visible on an edge or narrow side of thecassette, which allows that edge of the cassette to be plugged into aconnector or interface communicating with a pressure distributionmanifold. In this embodiment, the overall thickness T2 of the cassette,which includes the thickness of each of the midplate 134, first outerplate 144 and second outer plate 146, plus the width of the first 136and second 138 inter-plate spaces, allows pump or valve diaphragms to beseated on either the first or second side of the midplate, or both. Thispotentially increases the number of valve or pump stations that canpopulate a cassette having a given broad-side dimension. In thisembodiment, the overall thickness T2 of the cassette can be minimizedwhile maximizing the density of pump or valve stations that can beincluded on the cassette 132, with the excursion ranges of the encloseddiaphragms comprising a substantial majority of the overall thickness ofthe cassette. For example, in a cassette with such a ‘double-duty’midplate (allowing actuation channels and chambers on both sides of themidplate), nominal plate thicknesses of 2 mm, coupled with inter-platespaces that are 5 mm each to accommodate diaphragm excursions of 5 mm,results in an overall cassette thickness of 16 mm, nearly ⅔ of whichcomprises desired diaphragm excursion ranges.

FIGS. 12 and 13 show a dual-duty cassette midplate 150 in which each ofthe first 152 and second 154 sides of the midplate include bothactuation and liquid handling channels, incorporating actuation ports,actuation channels, actuation chambers, and liquid channels on each sideof the midplate. A plurality of valve stations 156 are shown in thisexample, although on-board pump stations can also be included in otherembodiments. In this respect, the cassette is similar to cassette 132 ofFIG. 12.

Optionally, this midplate 150 is additionally designed to be used in acassette assembly that incorporates outboard pump pods or liquid mixingpods whose volume requirements prevent including them as onboard pump ormixing chamber stations on an individual cassette. Where larger liquidstroke volumes are needed, two or more cassettes can be arranged so thatliquid or actuation lines can be connected to extension conduits 158,160 perpendicular to the face of the cassette that can connect toexternal pods situated between two cassettes. The conduits originate inthe cassette mid-plate (e.g. formed or molded with the mid-plate), andpenetrate either the first or second outer plate to provide for a directconnection to an external self-contained diaphragm pump, self-containedmixing chamber, or self-contained balancing chamber. If the conduits arerigid, they may also serve as structural members that help to hold thecassette assembly together. The perpendicular conduits may also be usedas liquid ports for connection to a fluid source or destination externalto the cassette. In this case, the conduit termination may beconstructed to make a connection with a flexible or malleable tube. Inthis type of cassette, the cassette actuation ports and initial portionsof the actuation channels can still all be located in the inter-platespace of the cassette, until they reach the point at which the fluid oractuation line must exit the cassette to connect to an associated podpump, balancing chamber pod or mixing chamber. With this configuration,the cassette assembly is a substantial improvement over previouslydisclosed cassette assemblies because of the more efficient arrangementof the cassette actuation ports. Since the actuation ports are alllocated along an edge of the cassette, the cassette can be pluggeddirectly into an associated pressure delivery manifold or a rigidreceptacle array without the need for flexible tubing connections andseparate connectors.

The cassette midplate 150 in FIGS. 12 and 13 also shows that actuationchannels and liquid channels can be routed from one side to the opposingsecond side of the midplate in order to increase the number of valve orpump stations that can be incorporated within a cassette of a particularsize. The routing of an actuation or liquid channel may be impeded bythe presence of other channels, pump stations or valve stations thatprevent a direct route from a cassette port to the destination valve orpump station. In that case, re-directing the actuation or liquid channelto the first/second side of the midplate may allow the channel to bypassan obstructing structure on the second/first side of the midplate. Thebypassing channel may simply make a single midplate penetration to theopposing side, or it may penetrate the midplate to bypass an obstructingstructure, and then return to the starting side of the midplate to reachits pump or valve station destination. FIG. 14 shows the second side 154of cassette midplate 150. An actuation port 162 arranged to supply valvestation 164 lacks an uninterrupted path to the valve station because ofthe presence of an extension conduit 168. Actuation channel 170 aconnected to cassette actuation port 162 terminates in an actuationchannel port 172 that penetrates the midplate 150. As shown in FIG. 13,actuation channel 170 b on the first side 152 of midplate 150 canconnect actuation channel 170 a with actuation channel 170 c viaactuation channel port 174, to complete the actuation channel pathwayfrom cassette actuation port 162 to valve station 164.

Whether a cassette includes actuation channels and chambers, as well asliquid channels, on both sides of the midplate (i.e. a dual-dutymidplate), a cassette can be arranged to have liquid cassette portslocated on a narrow side or edge of the cassette, so that a plurality orbank of such cassettes can be stacked together to form a compactcassette group. FIG. 15 is a rear perspective view of a cassette group176 comprising a plurality of individual cassettes 178 a-d stackedbroad-side to broad-side. Each cassette 178 a-d has one or more cassetteactuation ports 180 located on the narrow side of the cassette in thefirst inter-plate space 182 a-d, with the actuation ports facing in thesame direction so that the individual cassettes of the cassette groupcan be plugged into their respective corresponding connectors orreceptacle ports of a receptacle assembly, the connectors or receptacleports positioned next to each other and connected, mounted or attachedto a pressure distribution manifold.

The cassettes of a cassette group can be arranged to be in contact witheach other, whether or not they are fused or adhered to one another.Alternatively, they may be placed next to each other loosely or withsome spacing, so that each cassette of a group can be individuallyinserted or removed from its corresponding receptacle assembly withoutdisturbing the neighboring cassettes. This allows for individualcassettes to be placed on rails or tracks so that their actuation portscan be properly aligned with their respective connectors or receptacles,and so that they can more easily be inserted and removed. The cassettereceptacle assemblies can be located next to each other to provide for aspatially compact cassette group. Optionally, the cassette receptacleassemblies may be located within a single housing, which can providealignment and insertion/removal tracks for the individual cassettes. Oreach cassette receptacle assembly may be included in a separate housingfor the same purpose. In the setting of providing for individualizedfluid circulation to an array of objects, the arrangement allows for asingle cassette to be swapped out with a cassette having differentfeatures (with respect to number and distribution of pump and valvestations, and liquid flowpaths). Thus as the fluid circulationrequirements for any individual object change, the cassette groupconfiguration allows for convenient and rapid adaptation of a cassettewith the needs of its associated object. Furthermore, neighboringcassettes of a cassette group can be interconnected via their respectiveliquid ports by means of, for example, jumper lines. In this way,complex liquid mixing procedures can be carried out when solutions withparticular constituents at particular concentrations need to be providedto an object. Thus one or more cassettes of a cassette group can bededicated to a single object if desired.

FIG. 16 is a front perspective view of the cassette group 176 of FIG.15. In this example, for convenience of illustration the cassette liquidports 184 are located on a narrow side of each cassette 178 a-d oppositethat of the actuation ports 180. Although the actuation ports arepreferably arrayed on the same corresponding edges of the cassettes (sothat a pressure delivery manifold can be positioned behind the cassettegroup), the liquid ports of the individual cassettes need not all bepositioned along the same edges of the cassettes. In this embodiment,the cassette liquid ports 184 are positioned within the secondinter-plate spaces 186 a-d of the respective cassettes 178 a-d. Thecassette group 176 can thus be oriented so that it is facing externallyfrom one or more receptacle assemblies (not shown) connected, mounted orattached to a pressure distribution manifold. Each cassette 178 a-d iscapable of providing liquid circulation to a separate object, so thatthe number of individual cassettes in a group can be matched to an equalnumber of objects that require liquid circulation. For example, aplurality of biological cell stations, tissues or organs arrayed forgrowth, experimentation or testing can be supplied with circulatingliquids, drugs, nutrients or other chemicals by a plurality of cassettesin a cassette group, each cassette potentially providing each cellstation, tissue station or organ station with liquid solutions havingsimilar or different compositions. A cassette group such as cassettegroup 176 can also be configured to serve as a solution mixing station,with the liquid output of one cassette of the group providing the liquidinput of a neighboring cassette in the group, allowing for complexsolution mixing protocols. As such, two or more cassettes can bere-configured to serve a single object.

FIG. 17A shows a rear perspective view, and FIG. 17B shows a frontperspective view of a cassette group 186 that incorporates dual-dutymidplate cassettes 188 a-d. In other embodiments, a cassette group canincorporate one, two or more dual-duty midplate cassettes among one ormore single-duty midplate cassettes. In this case, representative secondinter-plate space 182 a-d actuation ports 190 and representative firstinter-plate space 186 a-d liquid ports 192 are shown. Depending on thenumber and size of the individual pump and valve stations in thecassettes 188 a-d, using dual-duty midplate cassettes may permit theplacement of a greater density of multi-purpose valve and pump stationsin a relatively confined space.

In some applications, the stroke volume or liquid chamber volume of apump or other type of chamber exceeds the volume that an on-board pumpor chamber can accommodate. In this case, outboard pump or chamber podshave been used, and positioned between two cassettes. Liquid linesand/or actuation lines arise from opposing faces of the two cassettes tosupply the outboard pumps or chambers, allowing liquid to flow, forexample from a first cassette to the outboard pod and then to the secondcassette, each cassette housing an upstream or downstream valve stationto control the flow of liquid. Or an outboard pump actuation line mayarise from the face of a first cassette, while the liquid inlet andoutlet line may arise from the opposing second cassette. This type ofcassette assembly also allowed for liquid lines to connect directly fromthe face of one cassette to the face of an opposing cassette. In priorimplementations, as shown in FIG. 18, the faces of the opposingcassettes 194, 196, 198 also included actuation ports 200 for theon-board pump stations and actuation ports 202 for the valve stations,along with liquid ports 204 and liquid 206 and actuation 208 lines tothe outboard pumps 210 or chambers 212. This arrangement led to a largenumber of flexible tube connections for both liquid and actuation linesplugged into the interior faces of the cassettes, which posed challengesfor manufacturing, assembly and servicing.

FIG. 19 shows a prior cassette assembly in which pneumatic actuationlines 214 ran from actuation ports 216 on the cassette faces 218 toblock-style connectors 220 a, b for subsequent connection to a pressuredistribution manifold used to operate the cassette assembly. This was inaddition to the liquid lines 222 that ran from liquid ports 224 on theindividual cassettes. This type of cassette assembly has beensubstantially improved by incorporating the cassette designs of thepresent disclosure.

Dialysis Cassette Assembly

FIG. 20 shows an example of a cassette assembly 226 that performssubstantially similar liquid-processing functions as the prior cassetteassembly of FIGS. 17 and 18, and serves to illustrate how the cassettesof the present disclosure substantially improve the construction,assembly and servicing of such a cassette assembly. In this example, thecassette assembly 226 shown is used for mixing, processing and movingdialysate solution in a portable hemodialysis apparatus. But uses forthis type of cassette or cassette assembly (i.e. cassettes havingedge-mounted actuation ports with actuation channels running betweenplates and parallel to the cassette face) are by no means limited tohemodialysis systems. As shown in FIG. 20, three cassettes 228, 230, 232are joined together by fluid-handling pods 234, 236. Theseinter-cassette pods may include self-contained diaphragm pumps havingboth actuation and fluid conduits, or other liquid-carrying chambers236, having only fluid conduits. Examples of other types ofliquid-carrying pods include fluid mixing chambers, or fluid balancingpods in which the flow through a first fluid line is balanced by theflow through a second fluid line through a pod having a first variablevolume separated from a second variable volume by a flexible diaphragm.Each fluid-handling pod 234, 236 fluidly connects to either or bothcassettes that flank it, either by flexible or rigid conduits. Rigidliquid conduits 238 may be preferred, because they can providestructural support for the cassette assembly. In the case of a diaphragmpump pod 234, both liquid-carrying and actuation conduits may extend toone or both cassettes flanking it. The conduits 238 penetrate the faceof the flanking cassette to reach a fluid or actuation channel locatedin the first or second inter-plate space of that cassette. Generally,actuation channels driving the inter-cassette pump pods will coursewithout interruption from a cassette actuation port to the actuationchamber of the pump pod. Fluid channels of either an inter-cassette pumppod or another type of fluid-handling pod will connect to acorresponding inter-plate fluid channel in one or both flankingcassettes via one or more diaphragm valves located in the cassette. Theactuation channels of these diaphragm valves, the actuation channels forthe pump pods, and any other actuation channel in the cassettes travelwithin the first or second inter-plate space of each cassette to a firstedge of the respective cassette to terminate into a cassette actuationport 240. In the cassette assembly, each cassette 228, 230, 232 hasactuation ports 240 located on a narrow side or edge of the respectivecassettes, and are all configured to face in the same direction, so thatthe cassette assembly actuation ports occupy one side of the cassetteassembly. This allows the cassette assembly 226 to be plugged into orunplugged from one or more receptacle assemblies in a single motion.With this arrangement, the need for flexible tubing to connect thecassette actuation ports to corresponding manifold output ports iseliminated. In the example shown in FIG. 20, cassette 228 is optionallyconfigured as a single-duty mid-plate cassette (in which all actuationports are located either in the first inter-plate space or the secondinter-plate space). In the same example, cassettes 230 and 232 areoptionally configured as dual-duty mid-plate cassettes, with someactuation ports located in both inter-plate spaces on either side of thecassette mid-plates 242, 244. Other arrangements are of course possible,depending on the fluid-handling tasks required of a similarly organizedcassette assembly.

FIG. 21 depicts a partially exploded view of the example cassetteassembly 226 shown in FIG. 20. The assembled cassettes 228, 230 and 232along with the inter-positioned pumps 234 or other liquid carryingchambers 236 are held in a frame assembly, to assure proper alignment ofthe cassette ports during installation and operation. Previouslydisclosed cassette assemblies could rely on the rigid conduits (e.g.conduit 238), and some retaining bars or springs to keep the assemblytogether (see FIG. 18), but did not require precisely aligned actuationports for directly plugging into a manifold assembly. In the presentlydisclosed cassette assembly, carrier frames 505 and/or 507 can eliminatethis concern by compactly securing the cassette assembly 226 andretaining it in the required configuration or alignment. Exemplaryembodiments in FIGS. 20 and 21 show a first carrier frame 505 and asecond carrier frame 507 that can engage with the cassette assembly 226from opposing directions. Some embodiments can provide similar carrierframes to secure the cassette assembly 226 from adjacent sides. Otherembodiments can also provide a monolithic carrier frame to secure thecassette from more than one pair of opposing sides.

Carrier frames 505 and 507 can further include plate rails that canslide over the corresponding cassette plates of cassettes 228, 230 and232 for engaging with the cassette assembly 226. Connecting the framecomponents together, and securing the enclosed cassette plates in railsmay eliminate the need for puncturing or drilling holes into any of thethree cassette plates in order to secure them to the frames. The railsconfiguration and absence of screws, nuts or clips through the cassetteplates can reduce the possibility of damaging the cassette assembly andinterfering with any of the pneumatic connections or pathways therein.For example, first carrier plate 505 can include a first set of platerails 505A, 505B and 505C and the second carrier plate 507 can include asecond set of the plate rails 507A, 507B and 507C. Plate rails 505A,505B, 505C, 507A, 507B and 507C can comprise elongated slots capable ofpartially or completely receiving at least one edge or a portion of theedge of corresponding cassette plates of cassettes 228, 230 and 232. Forexample, with reference to first carrier frame 505, the plate rails505A, 505B and 505C can receive edges of cassette plates of cassettes228, 230 and 232, respectively. In an embodiment, the rails can includecapping features. For example, rails 505A and 505C of the first frame505 can include capping features 505F and 505G positioned on the ends ofthe respective rails. Plate rails 507A, 507B and 507C can engage withthe cassette assembly 226 by receiving the edges of correspondingcassettes 228, 230 and 232. Moreover, walls of the plate rails 505A,505B, 505C, 507A, 507B and 507C can also optionally include notches 506configured to receive and cradle corresponding rigid liquid conduits 238when the carrier frames 505, 507 engage with cassette assembly 226.Plate rails 505A, 505C, 507A and 507D can have a closed end and an openend. The open end of the rails may be included to avoid interfering withnearby cassette ports 240. It should be noted that the first and secondcarrier frames 505 and 507 can slide onto the respective cassette edgesto engage with the cassette assembly 226 and may not require additionalfastening devices to engage directly with the cassettes 228, 230 and232. Additionally, securing features that supplement the rails i.e.features such as, but not limited to capping features 505F, 505G, andnotches 506 and 508 can further strengthen the engagement between thecassette assembly and the frames, thus allowing any force application onthe frame to be distributed more uniformly on the cassette assembly, andpotentially avoiding straining or distorting the cassette assembly 226.This arrangement can aid in compactly installing and removing thecassette assembly 226 from an array of manifold receptacles of thehemodialysis apparatus 246 without causing the cassette assembly torack, leading to misalignment of the cassette ports.

The plate rails 505A, 505B, 505C can be interconnected by an upper bar505D and a lower bar 505E that extend perpendicular to the plate rails.The lower bar 505E interconnects the plate rails 505A to 505B and 505Bto 505C at the open end of the rails and near the cassette ports 240.The upper bar 505D interconnects the plate rails 505A to 505B and 505Bto 505C at the closed end of the rails. Similarly, rails 507A, 507B,507C are interconnected by an upper bar 507D and a lower bar 507E thatextend perpendicular to the plate rails. The lower bar 507Einterconnects the plate rails 507A to 507B and 507B to 507C at the openend of the rails and near the cassette ports 240. The upper bar 507Dinterconnects the plate rails 507A to 507B and 507B to 507C at theclosed end of the rails.

At least one cross bar 511 can be positioned to connect the first andthe second carrier frames 505, 507 when the frames are positioned toengage with the cassette assembly 226. In this example, the cross bar511 is disposed longitudinally through the cassette assembly 226 andconnects the first and second carrier frames 505, 507 at opposing endsof the cross bar This arrangement helps to stabilize the side of theframes 505, 507 near the ports 240 of the cassettes 228, 230, 232. Thecross bar 511 helps to prevent the frames 505, 507 from shiftingposition with respect to the cassette assembly 226. Connection betweenrespective ends of the cross bar 511 and the corresponding carrierframes 505, 507 can be established by fastening features such as, butnot limited to, screws, bolts, adhesive, laser or ultrasound welding, orother similar fastening mechanisms. Optionally, the cassette assembly226 can provide alternative or additional connecting elements betweenthe first carrier frame 505 and the second carrier frame 507 to securethem to each other and the cassette assembly 226, including, but notlimited to, clips similar to clips 512 in FIG. 18, threaded rods, orzip-ties or other elements that limit the degree to which the frames505, 507 can shift with respect to each other.

FIGS. 20 and 21 further depict a first support plate 513 and a secondsupport plate 515. The first support plate 513 can be arranged tointerconnect the first and the second carrier frames 505, 507 in theirengagement with the cassette assembly 226. In the present example, thefirst support plate 513 is positioned on a side of the cassette assembly226 that is perpendicular to the sides on which the first and secondcarrier frames 505, 507 are located. Furthermore the first support plate513 is positioned on the carrier frame on a side opposite the cassetteports 240. First support plate 513 can additionally include flanges 513Aand 513B on opposing edges. These flanges 513A, 513B can be structuredto engage the upper bars 505D, 507D of the first carrier frame 505 andthe second carrier frame 507. The first support plate 513 may be securedto the upper bars 505D, 507D mechanically with clips, screws or thesupport plate 513 may be bonded to the upper bars 505D, 507D.Alternatively, the upper plate 513 and at least one of the frames 505,507 may be molded together. The first support plate 513 may engage theupper bars 505D, 507D when the carrier frames have engaged with theedges of the cassettes 228, 230, 232 of the cassette assembly 226. Thus,the first support plate 513 and the cross bar 511 may secure the firstand the second carrier frames 505, 507 to each other during theirengagement with the cassette assembly 226. The assembly comprising thecarrier frames 505, 507, cross bar 511 and first support plate securelyhold the cassette assembly 226, and help to more uniformly distributeexternal mechanical forces to the cassette assembly components to avoiddistorting their relative positions.

First support plate 513 can further provide an inner surface 513D (seeFIGS. 22A and 22B) facing the cassette assembly 226 and an opposingouter surface 513C, facing away from the cassette assembly 226. Duringinstallation of the cassette assembly 226, outer surface 513C of thefirst supporting plate 513 can interface with a cassette loadingapparatus (not shown) which is described below. The inner surface 513Dand outer surface 513C provide surfaces to which a cassette loadingapparatus can apply forces to move the cassette assembly as a unit.First support plate 513 can also provide alignment features toappropriately load and station the cassette assembly 226 in the loadingapparatus.

FIG. 21 also shows a second support plate 515 that can optionally beincluded to engage with one of the carrier frames 505, 507 to minimizetwisting or flexing of the frames. In the present example, secondsupport plate 515 is mounted to second carrier frame 507 and is attachedto the frame through connecting elements 519. The connection may beachieved by receiving the connecting elements 519 into correspondingconnecting junctions 520 provided on the second carrier frame 507. Inanother embodiment, the second carrier frame 507 can be integrated witha support plate such as, but not limited to the second support plate 515as a single component. Flexing or twisting of the first carrier frame505 can also be reduced by including a diagonal crossmember 523.Crossmember 523 can be integral to structure of the second carrier frame505 or can be attached on the frame separately. Additional supportelements similar to support plates 513, 515 and support bracket 523 canbe provided to supplement the carrier frames 505, 507 and retain therequired arrangement of the cassette assembly 226.

FIGS. 22A and 22B depict perspective views of an exemplary first supportplate 513. Flanges 513A and 513B can further provide engagement featuressuch as, but not limited to resilient clips or grippers 514. Firstsupport plate 513 can also include one or more clips 514 on non-flangedsides. Clips 514 can be constructed to engage edges of the carrierframes 505 and 507. For example, the clips 514 can be configured toengage the upper bars 505D, 507D. Alignment elements such as one or morenubs 516 (FIG. 21) may be included on edges of the carrier frames 505,507. Nubs 516 can serve as alignment features for slots 514B on thefirst support plate 513 to ensure appropriate alignment and connectionbetween the first support plate 513 and the carrier frames 505, 507. Inthe present example, the first support plate 513 may includelongitudinal and/or transverse stiffeners 517 to reduce mechanicallyinduced deformation of the first support plate 513.

FIG. 23 shows a hemodialysis apparatus 246 configured to enclose thecassette assembly 226. A front panel 248 is configured to include adialyzer recess and holder 250, a blood pump cassette receptacleassembly 252, and configured to hold a blood tubing set (not shown). Thedialysate cassette assembly 226 is configured to be housed within theenclosure of apparatus 246 behind the front panel 248.

FIG. 24 shows an enclosure 254 for the apparatus 246 of FIG. 23, withthe front panel 248 and other components removed. The internalconfiguration of the enclosure or housing 254 allows a cassette assembly226 to be positioned above internal shelf 256 of the enclosure 254. Theinterior of enclosure 254 (e.g. below the shelf 256) is arranged to holdother components, such as a heater for dialysate solution, tubing forvarious liquid flowpaths, a dialysate reservoir or tank, and one or moredevices to detect the conductivity and temperature of dialysate solutionat various stages of mixing. Behind this enclosure 254 is a recess 258arranged to hold a pressure distribution manifold (in this case apneumatic actuation manifold) with electromechanical valves, and one ormore electronic controllers, at least one of which is configured tocontrol the electromechanical valves of the manifold. These componentsare positioned outside the enclosure 254 to help shield them from hightemperatures that may be used when disinfecting the liquid-carryingcomponents of the hemodialysis apparatus 246. FIG. 25 shows a rearperspective view of enclosure 254, highlighting the recess 258, which islocated directly under shelf 256 of enclosure 254. Thus a pressuredistribution manifold can be positioned directly below a cassetteassembly 226, the cassette assembly being located within enclosure 254and the pressure distribution manifold being located outside enclosure254.

Loading and Locking the Cassette Assembly

FIGS. 30 and 31 depict installation and retention of the cassetteassembly 226 in the enclosure 254. In FIG. 30, the cassette assembly 226is lifted just above three cassette receptacle assemblies, with threearrays of cassette actuation ports 240 aligned with their respectivereceptacle ports on adaptors 266, 268, 270. The receptacle assembliesare configured to adapt the actuation port arrays of the cassetteassembly 226 with actuation outlets of a pressure distribution manifoldlocated outside the enclosure and below shelf 256. Lowering the cassetteassembly 226 allows the cassette actuation ports 240 to engage withtheir respective adaptors through a press-fit connection. Sealing of theindividual actuation ports 240 can be accomplished through the use ofO-rings, or gaskets with elastomeric wiper seals, or other meanstypically used in sealing press-fit connections. The adaptors in turncan provide a direct connection to output ports of the pressuredistribution manifold (FIG. 32 to FIG. 37) located below shelf 256 andoutside enclosure 254. FIG. 30 further depicts a cassette loadingapparatus 292 that can receive the cassette assembly 226 duringinstallation, and hold it in place. A handle 308 belonging to theloading apparatus 292, can operate to lock the cassette assembly insidethe enclosure 254. A detailed description of the operation of apparatus292 and handle 308 to lock and retain the cassette assembly is providedbelow with reference to FIG. 56 to FIG. 59. In one configuration, theloading assembly of FIG. 30 can be in an open position depicting theoperation handle extending parallel and away from the cassette assembly.FIG. 31 depicts the cassette assembly 226 locked in the cassettereceiving space by indicating the operation handle 308 to be angleddownward, moving the loading apparatus toward the receptacle assembliesof the manifold, and thus pressing the cassette assembly 226 into thecorresponding adaptor ports and securing it therein. In the presentexample, the loading apparatus 292 can comprise force applicationelements such as but not limited to, one or more bars that can interfacewith first support plate 513 (FIGS. 22A and 22B) and can be operated bythe handle 308. Lowering the handle 308 can allow the force applicationelements to push on the first support plate 513. This force can betransmitted to the cassette assembly 226 through the cassette frames505, 507, wherein the frames press the cassette assembly 226 towards theadaptors 266, 268 and 270. FIG. 31 depicts the cassette assembly 226 inthe operative configuration, i.e. the cassette assembly 226 is pressedto align the array of cassette actuation ports 240 with their respectiveadaptors 266, 268 and 270. It should be noted that the handle 308 inFIG. 31 is shown in a closed configuration i.e. the cassette assembly226 is locked inside the enclosure 254, with the handle positioned sothat the front panel of the hemodialysis device can be installed withoutinterference.

The embodiment of the hemodialysis apparatus 246 shown in FIGS. 45, 46comprises an enclosure 254 in which the footprint of the cassetteassembly 226 extends in a direction forward of—and overhangs—the shelf256. For this reason, a group of manifold interfaces or adaptors 266,268, 270 are configured to extend in a direction forward of the shelf256 as shown in FIG. 45. The adaptors 266, 268 and 270 provide therequisite mating of cassette assembly 226 actuation ports 240 to theirrespective connectors or receptacle ports 272 located on the interfacesor adaptors 266, 268, 270. Adaptors 266, 268, 270 in this example serveas receptacle assemblies, providing an array of receptacle ports formating with cassette ports 240 arrayed in each cassette 228, 230 and 232respectively. FIG. 46 shows a bottom perspective view of enclosure 254with installed interfaces/adaptors 266, 268, 270. The extent to whichthe adaptors overhang the enclosure shelf 256 (and therefore also thepressure delivery manifold 260) is apparent in this view. The adaptors266, 268, 270 serve to map the cassette ports arrayed in an extendeddirection along the edges of the individual cassettes to a morespatially compact array of manifold ports located in risers or topblocks 276A-C between the adaptors 266, 268, 270 and an upper block 274of the underlying pressure distribution manifold 272.

Pressure Distribution Manifold

FIG. 26 shows a schematic representation of an embodiment of a pressuredistribution manifold (or manifold assembly). This manifold assembly isarranged to selectively provide pneumatic pressure (positive, negativeor atmospheric) to control pneumatically-driven pumps and/or valves ontwo separate pump cassettes. In this improved embodiment, a first set ofpneumatic outlets is configured for direct connection to a first pumpcassette or cassette assembly (i.e. direct plug-in connection to themanifold assembly or to an adaptor directly connected to the manifoldassembly). In an embodiment, the direct-connection interface isillustrated schematically as one or more risers or ‘top blocks’ 276A,276B, which are positioned on a superior side of the manifold assembly260. The top blocks include direct-connection ports 261 configured toconnect directly with a first pump cassette (not shown), which can bepositioned directly above the manifold assembly 260. The manifold ormanifold assembly also includes a second set of pneumatic outletsconfigured for indirect connection to a second pump cassette viaflexible or malleable tubing. Also shown in FIG. 26 is an exemplaryfitting 582 for indirect connection to a second pump cassette (notshown), the connection configured for a flexible or malleable tube thattravels some distance away from the manifold assembly 260 to a remotelylocated second pump cassette. In the context of the presently describedhemodialysis device, the dialysate cassette assembly can be configuredto plug directly into the manifold assembly via ports 261, and the bloodpump cassette assembly (located more remotely on the front panel of thedialysis device) can be configured for pneumatic connection to themanifold assembly via flexible or malleable tubing to a plurality offittings (here represented by the exemplary fitting 582).

FIG. 26 also shows another improvement in a manifold assembly 260, whichhelps to prevent or reduce the accumulation of particulate or liquiddebris on internal sealing surfaces of electromechanical pneumaticcontrol valves. An exemplary valve 267 is shown in a generallyhorizontal orientation. Any internal valve seats or sealing surfaces areoriented to avoid having horizontal surfaces on which debris canaccumulate. In the schematic illustrations of FIGS. 26-29, a lower orbottom manifold block 272 mates with a middle manifold block 274. Thelower manifold block 272 has a cross-sectional ‘T’-shape (across thelong axis ‘Z’ of the manifold assembly 260), comprising a horizontalportion 272A and a drop portion 272B onto which a plurality of valvemounting surfaces and openings are arranged. An exemplary valve 267 isshown mounted to one such surface and over one such opening. A valveface seal (not shown) is assumed to interface the valve body with themounting surface of the drop portion of the manifold. The drop portion272B is shown for convenience to have a vertical orientation withrespect to the horizontal portion 272A. The drop portion 272B may alsohave a non-vertical orientation, such as one in which the valve mountingsurfaces and openings are angled in an upward direction, which orientsthe valve body and face seal in a downward angled direction.

This angled orientation will also help to prevent the accumulation ofliquid (e.g. liquid condensate) or debris on valve components havingsealing surfaces (e.g. valve seats). In many (but not all) valveembodiments, an associated internal valve plunger or piston will operatein a horizontal or near-horizontal direction, which is represented bythe valve 267 illustrated schematically in FIGS. 26-29.

In the examples shown in FIGS. 26-29, pressure source lines 263 areshown to be embedded within the lower or bottom manifold block 272.Depending on how the internal pneumatic channels in the manifoldassembly 260 are plumbed, these source lines can also be located in themiddle block 274. In the schematic illustrations shown, each of theplurality of valves 267 receives an input line from one of the pressuresource lines 263, and has an output line connected ultimately to anoutput port of the manifold assembly—either a direct-connect port 261 oran indirect-connect port 582.

FIG. 27 shows a schematic illustration of an embodiment of a manifoldassembly 260 in which the direct-connection blocks 276A, 276B overhang,are cantilevered or are offset with respect to the main body of themanifold assembly. In this illustration, the long axis (′Z″) of themanifold assembly can be made to accommodate a pump cassette of anyarbitrary length in the long-axis direction. But if the pump cassette isconfigured to also have an array of inlet ports that exceeds the mainfront-to-back (‘X’) dimension of the manifold assembly, thedirect-connection blocks can be arranged to overhang the manifoldassembly in that direction. Ports 261 can then be connected to channelswithin blocks 276A, B to be routed to a more compact array of one-to-onemapped ports on the top of middle block 274.

FIG. 28 shows a schematic illustration of an embodiment of a manifoldassembly 260 in which an array of pressure sensor ports 567 has beenpositioned between the direct-connection blocks 276A and 276B. In thiscase, various pneumatic channels within the manifold assembly can havebranch or in-line connections to sensor ports 567A of a pressure sensorarray 567. In most (but not necessarily all) cases, these channelsconnect to the output line of a pneumatic control valve, and to anoutput port of the manifold assembly to which the valve output line isconnected. In an example, an array of pressure sensing ports can beconfigured to mate with a printed circuit board (PCB) positioned abovethe array and including a corresponding array of pressure sensors. Thepressure sensors of the PCB can be connected to a hemodialysiscontroller that uses pressure information to control the pneumaticcontrol valves to deliver a pre-determined level and pattern of pressureto a pump or valve object in a connected pump cassette.

FIG. 29 shows a schematic illustration of an embodiment of a manifoldassembly 260 that includes one or more manifold adaptors or interfaceblocks 266, 268. In this example, top blocks 276A, 276B function asrisers to provide spacing between an installed direct-connection pumpcassette and the main body of the manifold assembly 260. The risers mayinclude pneumatic channels connecting a plurality of valves on themanifold (such as valve 267) to manifold adaptors or interface blocks266, 268 to ultimately connect to an associated pump cassette. Themanifold adaptors or interface blocks can be configured to spatiallyre-distribute output ports 261 a—that are relatively closely spaced in ariser block or in the other blocks of the manifold—to a differentlyspaced array or distribution of output ports 261 b. In this way, thedirect-connection output ports of the manifold assembly can be arrayedor re-distributed spatially to match corresponding input ports of amating direct-connection pump cassette. The manifold adaptor 266, 268thus includes transfer ports on a first side facing and mating with themanifold 274 or its associated riser 276A,B, which map intocorresponding transfer ports 261 b on an opposing second side facing andmating with a pump cassette assembly. A first array of manifold outputports having a first spatial port configuration can therefore bedirectly mated to a second array of cassette input ports having a secondspatial port configuration. The mapping between corresponding transferports is achieved through the routing of internal channels within themanifold adaptors 266, 268. In this case, the spatial array of themanifold or riser output ports has a length that is less than a lengthof the spatial array of the manifold adapter transfer ports on thesecond side of the adaptor. The result is that the manifold adapteroverhangs the front side of the manifold in a cantilever fashion. Thesefeatures help to disassociate the spatial and dimensional constraints ofa pump cassette assembly from those of a manifold assembly configured todrive the cassette(s) of the pump cassette assembly. In the currentembodiments, a manifold assembly can be made to be as compact as valve,channel and port constraints permit while retaining the ability tointerface with a pump cassette that may have substantially differentspace constraints or spatial array requirements of its actuation ports.

FIGS. 32, 33 show the details of one embodiment of a pneumatic actuationmanifold in the form of pressure distribution module 260. The pressuredistribution module 260 provides selectable pneumatic connection from aplurality of pressure sources to the cassette assembly that plugs intothe receiving ports on the platform of the manifold adaptors 266, 268,270. The pressure distribution module 260 may further provide selectablepneumatic connection to a remote cassette via flexible or malleablepneumatic lines (not shown). The pneumatic connections are selectivelycontrolled by digital or binary pneumatic valves 262, 265, 267 mountedin or on the manifold blocks. One or more controllers control the stateof the valves based on received signals from pressure sensors mounted onthe upper block 276 and in the case of a hemodialysis apparatus provideprogramed instructions to selectively activate valves and pump blood,dialysate and water in order to deliver a dialysis treatment to apatient.

The pressure distribution module 260 controls the action ofpneumatically-driven diaphragm pumps and pneumatically-driven liquidvalves by selective connection to one or more pressure reservoirs viadigital or binary electromechanical valves. The electromechanical valvesmay comprise two-way or three-way digital valves. The digital valves canhave two positions. A two-way digital valve is either open or closed. Athree-way digital valve connects a common port to either a first orsecond port. One or more controllers control the state of the valves262, 265, 267 based in part on signals received by the one or morecontrollers from pressure sensors 565 (see FIG. 34). The pressurereservoirs may include a high positive pressure reservoir, a lowpositive pressure reservoir, a negative pressure or vacuum reservoir,and a vent to atmosphere.

The pressure distribution module 260 may be assembled from a pluralityof manifold blocks. The pressure distribution manifold 260 in FIGS. 32,33 comprises a tee-shaped manifold block 272, a mid-manifold block 274and an end-manifold block 276. The pressure distribution manifold 260further comprises cartridge valves 265 mounted in the mid-manifold block274 and surface mount valves 267 that mount on the vertical leg of thetee-shaped manifold block 272. Disposition of the pressure reservoirports 263, first set of valves 265 and second set of valves 267 can behorizontal with respect to faces 272F, 274F and 276F (FIG. 33) belongingto manifold blocks 272, 274 and 276, respectively. This arrangement canhelp to avoid collection of debris or liquid in the valves that canpotentially impair their function or shorten their maintenance-freelife. Pressure sensors 565 (FIG. 34) are mounted to ports 567 on anupward facing surface of end-manifold block 276. The adaptors 266, 268and 270 provide ports 266P, 268P, 270P to receive the ports 240 of thecassette assembly 226.

The mid-manifold block 274 and Tee-manifold block 272 may includeinternal supply lines for atmospheric pressure, low positive pressure,high positive pressure and negative pressure. One or more of theseinternal supply lines run through the length of the manifold blocks 272,274. The ports for the internal supply lines are capped 264 or have aport 263 for a flexible tube connection to a pressure reservoir. Bothend faces of the manifold blocks 272, 274 may include ports to connectthe internal supply lines (not shown) to external pressure reservoirs.

A plurality of diaphragm pumps and diaphragm valves can be grouped in asingle cassette as shown in FIGS. 6-13. A plurality of such cassettesmay be joined together to form a cassette assembly 226 as shown in FIGS.20, 21. In this case the assembly spaces the cassettes apart in order toaccommodate outboard pumps, mixing chambers or fluid balancing chambershave volumes greater than can be accommodated within any one of theindividual cassettes. The pressure distribution module 260 includesadaptors 266, 268, 270 that extend at a right angle to the long axis ofthe manifold blocks 272, 274 276. The adaptors extend the interface areaof the pressure distribution module from the footprint of the manifoldblocks and risers to any area required to accept the ports 240 of thecassette assembly 226. Pneumatic layout and port distribution on andwithin the adaptors 270, 268 and 266 and its sub-components (not shown)allow direct connection between the cassette assembly 226 and themanifold blocks 272, 274, 276, with one-to-one mapping of each port ofthe cassette assembly with corresponding actuation ports of the manifoldassembly.

The external pressure reservoirs to which the pressure distributionmodule 260 may be connected may have volumes maintained at specified orpre-determined pressures by pumps controlled by a system controller. Inan embodiment, a high-pressure reservoir can be maintained at a pressureof about 1050 mmHg, and a positive pressure reservoir can be maintainedat a pressure of about 800 mmHg. The pressures actually delivered tovarious pneumatically actuated pumps and valves may vary based on thepressure reservoir ported by the two-way and three-way valves onpressure distribution module 260. Furthermore, intermediate pressuresmay also be delivered through a combination of rapid opening and closingof the on-off valves. Generally, a high pressure source may be usefulfor actuating diaphragm valves to ensure leak-free and reliable valveclosure during operation of the cassette assembly.

FIG. 33 depicts an exploded view of the pressure distribution manifold226. Manifold blocks 272, 274 and 276, can further comprise intermediaryelements connecting features among each of the manifold blocks 272, 274and 276. These intermediary elements and connection features can help inassembling the three manifold blocks and establishing pneumaticconnection between the individual manifold blocks 272, 274 and 276. Afirst set of intermediary components may include, for example, a firstplate 550, a first gasket 552 and a second gasket 554 that can beemployed between the T-shaped manifold block 272 and the mid-manifoldblock 274 and a second set of intermediary components may include asecond gasket plate 555, a third gasket 556 and a fourth gasket 558positioned between the mid-manifold block 274 and the end manifold block276. The two manifold blocks 272, 274 may be clamped together with agasketed mid-plate 550 between them. The mid-plate 550 may also bereferred to as a backing plate, as it provides a rigid surface thatforces the gasket to seal against multiple channels that may be providedon the end-manifold block 276, Tee-manifold block 272 and themid-manifold block 274. 2 Each manifold block 276, 274, 272 may compriseat least one face 276G, 274F, 272F (see FIG. 33, 35, 36) with channelsand various ports mating with ported plates and gaskets, such as plates550, 555 and gaskets 552, 554, 556, 558. The respective channels may beconfigured as grooves that include a solid bottom and two side wallswith an open top. The channel may be cut into one face 276F, 274F, 272Fof the manifold block or it may be formed with walls that extend abovethe surface of the manifold block face 276F, 274F, 274G and 272F. Asshown in FIG. 33, the open top of the channels may be sealed by clampinga gasket 554,552, 556, 558 backed by a rigid flat mid-plate 550, 555against the channels. In one example, the mid-plate 550 is a backingplate that forces the gasket 552 against all of the channels on face272F and gasket 554 against the channels on face 274G. Note that face274G is opposite face 274F in FIG. 33. The manifold block and gasket caninclude features to assure an essentially even distribution of pressureon the gasket. The mid-plate 550 provides a substantially smooth andrigid backing for the gaskets so that more than one manifold block maybe assembled or sandwiched into the multi-part pneumatic manifold 260.The channels are linked to pressure sources, valves, sensors and outletports that reside on other faces of the blocks. The manifold blocks 276,274, 272 may sandwich the gaskets 552, 554, 556, 558 and the mid-plate550, 555 between them with mechanical fasteners 570 to seal the multiplechannels on the channeled faces 272F, 274F, 274G, 276G of each of themanifold blocks 272, 274, 276. This sandwich construction allows thecompact assembly of multiple manifold blocks with sets of channels onone face of each block 272, 274, 276.

Connection points of the T-shaped manifold block 272 can be configuredto receive screws that extend through other components that assemble thepressure distribution manifold 260 as a unit. In this example, matchingconnection points 572 can be provided on the first gasket plate 550,connection points 573 on the mid-manifold block 274, connection points573 on the third and fourth gaskets 556, 558. The first set of valves265 can operate on pneumatic pathways within the manifold blocks 272,274 and 276 and/or the pneumatic pathways that connect the manifoldblocks 272, 274 and 276.

FIGS. 32 and 33 show an embodiment including a plurality of cartridgevalves 265 and the connections to the pressure reservoirs 263. Acartridge valve is inserted in a manifold port. Corresponding cavities(not shown) are formed to accommodate seals on the outside of thecartridge valves 265. The machined cavity may have a set of dimensionsdefined by the manufacturer of the valve to assure sealing and properfunctioning of the cartridge valve 265. Although in other embodimentsthe numbers may vary, in this particular embodiment, approximatelyforty-eight cartridge valves 265 mount on a side face of themid-manifold block 274. This side of the mid-manifold block 274 isperpendicular to the channeled face 274F. In some embodiments, thecartridge valves are three-way valves, such as Lee LHDA Plug-In valvesavailable from The Lee Company USA, Westbrook, Conn. The number ofelectromechanical valves is determined by the number of individualdiaphragm pumps and valves to be operated in the direct-connect cassetteassembly and a remote-connect cassette assembly (if desired), and thelinear array of the electromechanical valves results in the extendedlength of the manifold assembly.

Referring now to FIG. 34, the pressure distribution manifold can serveas a pneumatic actuation device for components other than the cassetteassembly 226. For example, pressure distribution manifold 260 can alsobe in pneumatic communication with other pneumatically driven valves,diaphragm pumps, pneumatic cylinders and remote cassettes that comprisediaphragm valves and diaphragm pumps. In one example, the pressuredistribution module 260 controls the position of an occluder 251 in FIG.23, the occluder comprising a pinch valve to block the blood lines, anddriven by a pneumatic cylinder. In another example, the pressuredistribution module 260 can be placed in pneumatic communication with adialysate tank in order to make volume measurements of the tank usingpressure information. Further, the pressure distribution module 260 maybe arranged to control the pumping action of a blood pump cassette (notshown) that mounts on the blood pump cassette receptacle assembly 252 inFIG. 23. Referring now to FIG. 34, the ports 582 shown on the T-shapedmanifold block 272 can be connected with one or more blood pumpcassettes directly or through flexible or malleable tubing to establishthe required pneumatic connection. The ports 582 include fittings thatconnect to a pneumatic tube and may be individually removable from thetee-shaped manifold 272. The pneumatic lines connected at one end toports 582 may connect at a second end to a connector on the surface ofthe wall 255 (FIG. 24) of the dialysis machine. A second connectorinside the housing may then make a connection using flexible tubes to,for example, a dialysate tank, a pneumatically actuated tubing occluder,and/or to a blood pump cassette receptacle assembly 252.

The cartridge valves 265 and the surface mount valves 267 in thisexample control the pneumatic pressure delivered to the occluder, bloodpump cassette and other pneumatically driven items in the hemodialysismachine 246. Mounting features such asstandoffs 580 can be provided toattach the pressure distribution module 260 to the back wall of theenclosure 254 and set the location of the adaptors 266, 268, 270relative to enclosure 254.

Continuing to refer to FIG. 34, 35, valves 267 disposed on the T-shapedmanifold block 272 are electromechanical valves that seal against a flatsurface or a surface machined to accept the valve face. In someembodiments, the surface mount valves 267 can be proportional valves, orcontinuously variable valves (also referred to as ‘vari-valves’). Inother embodiments, the surface mount valves 267 are binary two-way orthree-way valves. In some examples, surface 272F is generallyhorizontal, making the leg of the T-shaped cross-section of manifold 272generally vertical. In a preferred arrangement, valve mounting surfaceof the leg is either vertical or tilted slightly upward, so that portson the valve 267 are either horizontal or tilted downward to avoidcollection of debris or liquid. Sealing features such as O-rings and/orother elements can be provided on the valves to prohibit leakage offluid or air. The valves may be any digital two-way or three-way valvesuitable for surface mounting, such as, for example, model11-15-3-BV-12-P-0-0 from Parker Hannifin Corporation in Hollis, N.H.

Referring now to FIG. 34, the pneumatic flow on the pressuredistribution manifold 226 can be monitored through one or more pressuresensors, these sensors can be mounted on a sensor board (e.g. PCB). Inthe present example, the sensor board 560 can be positioned over asurface 567 of an upper manifold block 276, in spaces between the risers276A-C. The pressure sensors 565 may be directly mounted to the face276F of the first end-manifold block 276. The pressure sensors 565 maybe integrated circuits soldered to a printed circuit board (PCB) 560. Asshown in FIG. 34, a printed circuit board 560 including one or morepressure sensors 565 may be mounted on the top face 276F that isparallel to the channeled face of the second end-manifold block 276 witha gasket to pneumatically isolate each sensor, and with a plate (notshown) to hold the PCB 560 in place and compress the gasket sufficientlyto seal each pressure sensor from the atmosphere. The sensor board 560can be coupled with the surface 567 of the end manifold block thoughfastening components such as screws, nut-bolt pairs, rivets, adhesive ora combination of such fastening mechanisms. An example pressure sensor565 may be obtained from Freescale Semiconductor, Inc. in Tempe, Ariz.(part no. MPXH6250A). The PCB including a plurality of pressure sensors565 may be mounted as a unit to the end-manifold block 276. The pressuresensing face of each pressure sensor 565 may be fluidly connected to thedesired pressure sources such as reference volumes or more remotely tothe actuation chambers of diaphragm pumps, or to a dialysate reservoirtank. In some cases the sensors are arranged to monitor liquid pressuresin various diaphragm pumps of the liquid handling cassettes. Theend-manifold block 276 provides risers 276A, 276B and 276C that caninterface with the respective adaptors 270, 268 and 266. The manifoldassembly is constructed so that the sensor board 560 avoids interferingwith the engagement between the risers and the corresponding adaptors.The risers also provide separation between the liquid handling cassetteassembly above and the temperature sensitive sensor board 560, allowingfor placement of insulation 269A between the two.(see, e.g., FIG. 48).

FIGS. 36 and 37 illustrate the second manifold block 276 with a face276F and a base surface 276G. Base surface 276G can be configured tomate with one or more intermediary components such as gaskets, gasketplates and/or other manifold blocks. As shown, the base surface 276 cancomprise a plurality of pneumatic channels 574 that are sealed by gasket558 (FIG. 33). In some examples, the channels 574 may connect pressureports 567 on face 276F to holes 261A, 261B, 261C in the risers. In otherexamples, the channels 574 may connect pneumatic pathways or holesthrough the gasket 558 to either the pressure ports 567 or holes 261A,261B, 261C. Face 276F can comprise the risers 276A, 276B and 276C thatcan serve as mounting surfaces for corresponding adaptors 270, 268 and266, respectively. Pneumatic ports 261A, 261B and 261C, on the risers276A, 276B and 276C, can interface with the respective adaptors 270, 268and 266 for transmitting pneumatic pressure to the cassette assembly226. Secure connection between the riser ports 261 and the adaptors canbe established via mechanical fittings such as nut-bolt pairs, threadedor push-screws or similar mechanisms. The mechanical assembly can alsoinclude mating of the blocks with intermediary components such as one ormore gaskets 568 (FIG. 32), gasket plates and/or similar components.

Pneumatic Connections in Manifold

The structure and function of the manifold 260 in FIG. 32 can be furtherunderstood by examining the pneumatic pressure sources, conduits,valves, sensors and exit ports of manifold 260. In an example presentedin FIG. 32, the manifold 260 has tens of valves, sensors and ports. Thefollowing section describes 3 exemplary pathways that comprise sources,valves, conduits, ports and in one example a pressure sensor. Theexample pathways serve to illustrate how elements of the manifold inFIGS. 32 and 33 come together to provide selectable fluid connectionsbetween pressure sources and actuation chambers of pneumatically drivenvalves and pumps, and provides fluidic connections to pressure sensors.The pressure sensors provide information to a controller that controlsthe valves in order to safely pump blood, dialysate and water to providetherapy to a patient.

The pneumatic manifold schematic in FIG. 38 describes the pneumaticconnections to a blood pump cassette. (The blood pump cassette in thiscase is located on a front panel of the dialysis unit, so it connects tothe manifold using flexible tubes rather than a direction connection).The pneumatic circuits in FIG. 38 selectively connect the actuationchambers of the blood, and heparin pumps and associated valves to thehigh positive pressure source HP, low positive pressure source LP ornegative pressure source NEG. The circuit 1005 connects a blood pump BP1to a pressure sensor P_BP1, the low pressure source LP via valveV_BP_POS1 and the negative pressure source NEG via valve V_BP_NEG1.

The blood pump actuation circuit 1005 in the manifold 260 is presentedin FIGS. 39, 40. The flowpaths are the holes and channels of the variousblocks of manifold 260. The low pressure source LP is a conduit inhorizontal portion 272A of Tee manifold that runs the length of the Teemanifold block 272. The negative pressure source NEG is a conduit thatparallel to LP through the long axis of the Tee manifold block 272.Positive pressure flows from the LP conduit through flow channel 1012that is located on top of the Tee manifold 272, then through a hole 1020through the vertical leg 272B of the Tee manifold to theelectromechanical valve V_BP_POS1. When the valve V_BP_POS1 opens, thepositive pressure flows up through hole 1025, which is in the verticalleg 272B to channel 1040 located on top of the Tee manifold 272. The lowpressure then flows through hol 1060 to port 582, where a fitting allowsfor a flexible or malleable line to connect the port to the (remote)blood pump cassette. The pressure in the blood pump connected to port582 is monitored by a pressure sensor mounted to port P_BP1. Port BP1 islocated on the lower of the two upward facing surfaces of the topmanifold block 276. The port P_BP1 is fluidically connected to channel1040 via hole 1057 in the top manifold block 276, a channel 1055 on thetop of mid manifold block 274 and a hole 1050 through the mid manifoldblock 274.

Shown embedded in the manifold assembly 260 in FIG. 40, in circuit 1005,the Tee manifold block 272 selectively connects an actuation chamber ina blood pump cassette (plugged into cassette receptacle 252 in FIG. 23)to either the low pressure source LP or the negative pressure source NEGvia two valves. A pressure sensor mounted to the top manifold block 276is fluidically connected through holes and channels in the top and midmanifold blocks. Other pneumatic circuits may connect actuation chambersfor the diaphragm pumps in the cassette assembly 226 to two of the lowpressure LP, atmospheric ATM and negative pressure NEG sources viavalves on the vertical leg 272B of the Tee manifold block 272.

The pneumatic schematic in FIG. 41 describes the pneumatic connectionsto the various actuation ports of the cassette assembly 226. Thepneumatic circuits in FIG. 41 selectively connect the actuation chambersof the various valves (and the two diaphragm pumps that happen to beillustrated here) on an outer dialysate cassette (ODC) to at least oneof the atmospheric pressure ATM, high positive pressure source HP, lowpositive pressure source LP, and negative pressure source NEG. Circuit1100 is an example pneumatic circuit that connects the diaphragm valveV_MIX_DT in the ODC cassette to either the ATM or LP pressure sourcesvia a 3 way valve 1105. Circuit 1200 is an example pneumatic circuitthat connect the liquid valve V_DISINECT in the ODC cassette to eitherthe HP or NEG pressure sources via a 3 way valve 1205.

The Mix_DT valve circuit 1100 and the DISINFECT valve circuit 1200 inthe manifold 260 are presented in FIGS. 42, 43. The flowpaths comprisethe holes and channels of the various blocks of manifold 260. Thepressure sources, ATM, NEG, LP, HP, are conduits arranged along the longaxis of the mid-block 274. The MIX_DT circuit 1100 connects either thelow pressure source LP or the atmospheric source ATM to the outlet portV_MIX_DT for the MIX_DT liquid valve in the cassette assembly 226. Thelow pressure source LP is connected to the valve 1105 via a channel 1110on the bottom face of the mid manifold block 274 and hole 1115. Theatmospheric source ATM is connected to the valve 1105 via a channel 1140on the bottom face of the mid manifold block 274 and hole 1145. Thevalve 1105 is connected to the outlet port V_Mix_DT via channel 1120 onthe top of the mid manifold block 274, hole 1130 through the topmanifold, and hole 1135 through the adaptor 268.

The DISINFECT circuit 1200 connects either the high pressure source HPor the negative source NEG to the outlet port V_DISINFECT for theDISINFECT liquid valve in the cassette assembly 226. The high pressuresource HP is connected to valve 1205 via a channel 1210 on the bottomface of the mid manifold block 274 and hole 1215. The negative sourceNEG is connected to the valve 1205 via a channel 1240 on the bottom faceof the mid manifold block 274 and hole 1245. The valve 1205 is connectedto the outlet port V_DISINFECT via channel 1220 on the top of the midmanifold block 274, hole 1222 through the mid manifold 274, channel 1224on the bottom of the mid manifold, hole 1226 back through the midmanifold, channel 1228 on top of the mid manifold, hole 1230 through thetop manifold 276 and through the adaptor rail 268 via hold 1235 andchannel 1237.

FIG. 43 shows how the circuits above are physically embedded withinmanifold assembly 260. Also shown is the mapping of these actuationports from an array on the riser 276B to a spatially different array ofactuation ports of manifold adaptor 268, providing an actuation portarray that matches the actuation port array of the cassette assembly226.

FIG. 44 illustrates the pressure distribution manifold 260 installed inthe recess 258 of enclosure or housing 254. This arrangement can allowappropriate alignment between the ports 261 on the risers of thepressure distribution manifold 260 and the respective ports on themating surface of the adaptors 266, 268 and 270. In the presentembodiments, the manifold 260 is positioned below some thermalinsulation 264. Insulation 264 can be provided between the body of themanifold 260 and the shelf 256. This arrangement isolates thetemperature sensitive electronics from heated fluids circulating incomponents inside the enclosure or housing 254.

As shown in FIG. 45, in this embodiment of the hemodialysis apparatus246 and enclosure 254, the footprint of the cassette assembly 226extends forward from a front face of the apparatus 246. With referenceto a user or operator facing the hemodialysis apparatus 246, the thecassette footprint extends over the front edge of the shelf 256. Forthis reason, one or more adaptors 266, 268, 270 are configured toprovide the requisite mating of cassette assembly 226 actuation ports240 to their respective connectors or receptacle ports 266P, 268P and270P located on the interfaces or adaptors 266, 268, 270. Adaptors 266,268, 270 in this example serve as receptacle assemblies, providing afirst spatial array of receptacle ports for mating with identicallyarrayed cassette ports 240 of each cassette 194, 196 and 198respectively of the cassette assembly 226. FIG. 46 shows a bottomperspective view of enclosure 254 with installed interfaces/adaptors266, 268, 270. The extent to which the adaptors overhang the enclosureshelf 256 (and therefore also the underlying pressure delivery manifold246) is apparent in this view.

FIG. 32 shows how adaptors 266, 268, 270 are mounted to the top side ofmanifold risers 276A-C, and how they overhang the front side of manifold260. The first spatial array of receptacle ports 266P, 268P and 270Pconnect with a second (in this case more compact) spatial array ofoutput ports 261 of the top block or riser 276A-C of the manifold 260.Internal channels within the adaptors 266, 268, 270 are routed to therespective risers 276A, 276B and 276C mounted above a correspondingarray of manifold output ports. FIG. 52 shows the manifold/adaptorassembly with adaptor 266 removed and exploded to fully reveal theconstruction of the adaptors, as well as risers 276C, 276A and 276B.

FIGS. 47, 48 are rear views of manifold 260, and illustrate that risers276A, 276B and 276C allow adaptors 266, 268, 270 to be slid into theirrespective positions in enclosure 254 from the rear of the enclosure viaslots or cutouts 280, 282, 284 of the shelf 256 of enclosure 254. Therisers 276A, 276B and 276C are made sufficiently tall to allow for theplacement of insulation—either rigid foam insulation or other types ofinsulation—to provide a thermal barrier between the shelf 256 and thebody of the manifold 260, as well as the electronic components (controlboards, sensors, etc.) located in recess 258. (See, e.g., insulation269A wrapped around the risers in FIG. 48). FIG. 48 shows how anassembly comprising manifold 260, its attached risers and adaptors 266,268 and 270, along with other related components, can be slid intoposition as a group into the recess 258 of enclosure 254.

FIGS. 49 to 51 illustrate engagement between the adaptors and theirrespective rails wherein the adaptors are located within the enclosureto receive the cassette assembly from the cassette loading apparatuswithin housing 254. Adaptor receptacles or adaptor rails 591, 593 and595 may be integrated with shelf 256 of the enclosure 254 or can beseparate component/s that can mechanically attach to the enclosure 254.In one embodiment, shelf 256 includes spaces to receive or attach theadaptor rails 591, 593 595. FIG. 48 specifically depicts a rear(outside) view of the enclosure 254 with adaptors 266, 268, 270partially inserted into respective adaptor rails 595, 593 and 591 (shownin FIG. 49). The manifold 260 is attached to the adaptors 266, 3268, 270before the manifold/adaptor assembly is slid into its final location inthe enclosure 254 as defined by the adaptors and adaptor rails. As shownin FIG. 49, the rails 591, 593 and 595 are located in the spaces 591S,593S and 595S respectively. FIG. 49 depicts a front (inside) view of theadaptors 266, 268 and 270 partially received into their respectiveadaptor rails in the enclosure 254.

Proper alignment of the adaptors 266, 268, 270 and the pneumaticmanifold 260 can be important to ensure that the plurality of pneumaticports 240 of the cassette assembly 226 align with the matchingreceptacle ports 266P, 268P, 270P to provide the necessary pneumaticconnection to cassette assembly 226. The final positioning of theadaptor is defined by adaptor rails that are positively mounted on thesame enclosure that mounts the cassette loader 292 on the roof of theenclosure 254. As a result, the retaining mechanisms for the abovementioned components should be appropriately positioned to achieve thealignment of pneumatic ports between the three assemblies i.e. thecassette assembly 226; the adaptors 266, 268, 270 and the pneumaticmanifold 260. FIG. 50 depicts a cassette loader 292 with an operatinghandle 308. The cassette loader 292 can be mounted on an inner surfaceof a roof 604 of the housing or enclosure 254. As illustrated, thecassette loader 292 and the adaptor rails 591, 593 and 595 arepositioned on opposing surfaces of the enclosure 254 and maintain afixed spatial relationship with each other.

FIG. 51 depicts an example adaptor rail 591 that can comprise ahead-rest or flange 592 and a tray portion 597 with a raised platform596 that can partially of completely occupy the tray portion 587. Headrest 592 with the tray portion 597 forms a frame of the rail 591. Thetray portion 597 can receive the corresponding adaptor, and thecorresponding adaptor can rest on the raised platform 596. The trayportion 597 can also comprise fencing contours 594 that can be curvedaccording to the edges of the corresponding adaptor received in the rail591, such that the adaptor can slide down into the receiving rail. Inthis embodiment, the tray portion 597 can further provide a cut-outregion 597 where the received adaptor can interface with a correspondingriser on the pneumatic manifold 260. Elongated slots or grooves 611 mayoptionally be provided between the sides of the raised platform 596 andthe fencing contours 594. Elongated grooves 611 can collect any leakingliquid and help to divert any leaking liquid or condensation away fromthe top surface of an installed adaptor, which might risk reaching theelectronics disposed below the shelf 256 or in the recess area 258.

FIGS. 52 and 53 depict an exploded view of an example adaptor 266 andits interaction with the corresponding riser 276C. More specifically,FIG. 52 depicts a top down view of the plurality of plates and gasket/sthat can collectively form the adaptor 266. And FIG. 53 depicts a bottomup view of the same exploded view of adaptor 266. An adaptor is arrangedto provide individual pneumatic pathways between the first port array ofcassette assembly 226 and the second port array of pneumatic manifold260. In this example, the pneumatic ports 240 on the cassette assemblyare distributed over an extended surface area away from the narrowdimension of the manifold assembly 260. The adaptor acts to convergethis first larger spatial array into a smaller spatial array of thepneumatic ports 261 on the risers of the manifold 260. As illustrated inFIGS. 52 and 53, exemplary adaptor 266 can comprise a plurality oflayers or plates comprising pneumatic openings and channels thatconverge to a smaller surface area as the layers progress towards therespective riser. Top plate 280 of the adaptor 266 includes pneumaticports 271 and connecting features to engage with the subsequent platesof the adaptor. Pneumatic ports 271 and connecting features 293 can beseen through the top view of the top plate 280 in FIG. 52, and throughthe bottom view of the top plate 280 as shown in FIG. 53. Top plate 280rests on an intermediate block 286 that includes corresponding pneumaticports 285 on its first surface 286A. These pneumatic ports 285 coincidewith the pneumatic ports 271 on the top plate 280. A wiper gasket 282can be received into a gasket receptacle 281 recessed into a firstsurface of the intermediate block 286. The continuous elastomeric gasket282 can be formed from a mold, with appropriately located wiper seals284. The wiper seals 284 provide a sufficient sealing engagement betweencassette ports 240 and corresponding adaptor receptacle ports 271, whileproviding lower frictional resistance to the installation and removal ofcassette assembly 226 than, for example, individual O-ring seals.

FIG. 53 depicts a second opposing surface 286B of the intermediate block286. This surface includes pneumatic channels 286C in fluidcommunication with the ports 281 on the first surface 286A. Channels285C can be laid out to converge and connect the pneumatic ports 281 onthe first surface 286A to the pneumatic ports distributed on the secondsurface 286B. As depicted, the pneumatic ports on the second surface286B occupy a smaller area and different spatial array compared to thepneumatic ports on the first surface 286A. The channels 285C ensure thatthe pneumatic ports 281 converge or shift toward the port array of theriser side of the adaptor 266. A second intermediate block 290 caninclude pneumatic ports 288 to coincide with the array of pneumaticports provided on the second surface 286B of the intermediate block 286.A second gasket 289 can be positioned between the first intermediaryblock 285 and the second intermediary block 290. Gasket 289 can allowappropriate sealing between the first intermediary plate 286 and thesecond intermediary plate 290, and allow the gasket to be compressed toan extent required to create a seal. In one embodiment, a set ofalignment features can be provided on the gasket 289 as well as on oneor both of the adjoining plates. In this case the plates can be thefirst intermediary block 286 and the second intermediary block 290.Moreover, a transitional gasket 289 can include pneumatic portscorresponding to the pneumatic ports 285 on first intermediary block 286and the pneumatic ports 288 on the second intermediary block 290. Ariser gasket 291 can be positioned between the second intermediary block290 and the corresponding riser, which in this example is riser 276C.This gasket is arranged to seal the interaction between the secondintermediary block 290 and the riser 276C. A plurality of gasketalignment features can be provided on mating surfaces of the secondintermediary bock 286 and the riser 276C. The preceding discussion ismeant to also apply to the adaptors 268, 270 and the interacting risers276B and 276A. Number and spatial distribution of pneumatic ports on theother adaptor-riser interaction embodiments can differ, and in thisembodiment do differ.

Sealing components between ports typically include O-rings when there ispneumatic interaction between the ports. In case of the adaptors, aplurality of O-rings can be used to ensure a sealing engagement betweenthe mating ports. However a plurality of spatially arrayed O-rings canexhibit relatively poor alignment tolerances when a plurality ofpneumatic ports 240 are inserted into the corresponding adaptor ports.In addition to tolerance issues, a plurality of O-ring connections maycreate a greater than desirable engagement/disengagement force betweenthe cassette assembly 226 and its associated adaptors. In an alternativearrangement, a web of wiper gaskets can be employed to make the requiredseal, and can be installed between two interacting plates or blocks ofan adaptor. FIG. 53 illustrates an exemplary wiper gasket 284 that canbe molded as a single unit, thereby substantially simplifying assemblyand installation procedures. FIG. 54 depicts an exemplary wiper gasketused in one of the manifold adaptors. FIG. 55 shows a cross-sectionalview 33H of the wiper gasket of FIG. 54. As illustrated, gasket 284 canbe formed to annularly encircle port 285 and form a conical peripheryrecess toward the pneumatic port 285. Gasket 284 can optionally includean annular nodule or ridge 283 constructed into the wiper gasket 284 tocover a portion of the port 285. This arrangement and construction ofthe wiper gasket 284 may allow insertion of the cassette ports 240 withan acceptable amount of force, and can also ensure sealing between theadaptor and cassette during operation (i.e. during application ofpositive and negative pressure through the ports of the adaptor).

FIG. 56 and FIG. 57 show a cassette seating apparatus or cassette loader292 used to secure a first side of cassette assembly 226 in order tomove the cassette assembly linearly toward or away from one or morearrays of receptacle assemblies arranged to mate with a correspondingarray of cassette ports 240 on one or more of cassettes 228, 230 and 232on an opposing second side of cassette assembly 226. In the exampledescribed below, the receptacle assemblies comprise manifold adaptors266, 268, 270, but the cassette loader can be used in any other systemin which a ported cassette is to be plugged in and out of any type ofreceptacle array, including, for example, a fixed multi-port receptacleor a moveable connector equipped with an array of ports, among otherpossibilities. The receptacle ports to which cassette actuation portsconnect can also be arranged on a frame, housing or even directly on amanifold output port array, rather than the exemplary adaptors 266, 268,270 shown, if the two sets of mating ports can be arranged to beproperly aligned. The cassette seating apparatus 292 has a genericutility in assisting a cassette with external ports to engage with ordisengage from mating connectors or receptacle ports on any device.

FIG. 56 shows cassette loader 292 in a retracted position, which movesthe cassette assembly linearly away from receptacle ports 261 b of FIG.29, or ports 266P, 268P and 270P of FIGS. 30, 32, 45, or more generallyports 271 of FIG. 52, which in this example are arrayed on adaptors 266,268, 270. Note that cassette seating apparatus or cassette loader 292can be used to seat or unseat a cassette or cassette assembly onto orfrom a receptacle assembly, as long as a single cassette or group ofcassettes has either liquid or actuation ports on a side opposite thatof a side secured by the cassette seating apparatus 292.

In this example, the cassette seating apparatus 292 comprises astationary frame 294 that includes stationary members 296 a,b.Stationary members 296 a,b are coupled to a linkage that in turninteracts with a movable cassette mount 298. Movable cassette mount 298is configured to hold a cassette or cassette assembly, and in thisexample comprises a flange 300 a,b leading to a cassette mount rail 302a,b. In this example, cassette mount rails 300 a,b allow a cassette orcassette assembly to be slid into position on the seating apparatus 292,and held. Other examples can include a clamping apparatus that can graspthe cassette or cassette assembly. In this example, independent movementof an installed cassette or cassette assembly is limited by the presenceof one or more crossmembers 304 limiting top-side movement of theinstalled cassette or cassette assembly, and by actuator arms 306 a,b ofan operating handle 308, the actuator arms 306 a,b moving into aposition to interfere with lateral movement of an installed cassette orcassette assembly.

As shown in FIGS. 56-58, the linkage may comprise two or more swing arms310 a,b, each said swing arm pivotably connected 312 on a first end tostationary members 296 a,b. Each of the swing arms 310 a,b is arrangedto move in a plane generally parallel to the direction of motion ofcassette mount 298 with respect to stationary member 296 a,b. A secondend of each swing arm 308 a,b comprises a hub 316 coupled to an axle orpinion 318, the axle/pinion configured to interact with flange 300 a or300 b that is generally parallel to a plane of motion of the swing arm310 a,b. The axle or pinion 318 is positioned within an elongate slot320 in the flange 300 a or 300 b that translates an arcuate motion ofthe second end of the swing arm 310 a,b toward or away from stationarymember 296 a,b into a linear motion of the cassette mount rail 302 a,302 b toward or away from the stationary member 296 a, 296 b. In thisexample, axle or pinion 318 optionally extends from flange 300 a toflange 300 b to also serve as a crossmember 304. Axle or pinion 318 caninteract slidably with slot 320, or by other means (such as, for examplethrough a circular bearing or wheel positioned in slot 320).

To help ensure linear motion of cassette mount 298, one or more guideelements (such as, e.g. post 322) can optionally be included to limitlateral movement of cassette mount 298 and its attached mount rails 302a,b. A guide element 322 can be rigidly attached or mounted tostationary frame 294 (or alternatively stationary members 296 a,b), andextend in the desired direction of movement of cassette mount rails 302a,b. The guide element 322 can interact with cassette mount 298 (oralternatively flange 300 a or 300 b, or mount rail 302 a or 302 b),through a guide hole 324 (or a guide rail, track or other element) thatconfines the relative movement of cassette mount 298 to a fore and aftdirection with respect to the frame 294 or stationary members 296 a,b.

FIG. 56 shows the cassette seating apparatus 292 in a nearly fullyretracted position, with cassette mount 298 retracted away from anassociated receptacle assembly sufficiently to disengage cassetteactuation (or liquid) ports of an installed cassette from theirrespective receptacle ports. (See, e.g., FIGS. 30, 31). FIG. 57-59 showsthe cassette seating apparatus 292 in an engagement position, with thecassette mount extended linearly away from stationary frame 294 orstationary members 296 a, 296 b sufficiently to engage cassetteactuation (or liquid) ports of an installed cassette with theircorresponding receptacle ports. Actuator arms 306 a,b of handle 308 arepivotally connected on a distal end 326 to stationary members 296 a, 296b. Each actuator arm 306 a,b is also pivotally connected on a moreproximal portion 328 of the arm 306 a,b to a first end of a connectingmember 330 a,b. A second end of connecting member 330 a,b is thenpivotally connected to an actuator bar 332 having a pivotal connectionto the second end of each swing arm 310 a,b comprising the linkage ofcassette seating apparatus 292. Connecting member 330 a or 330 b moveseccentrically with respect to the axis of rotation of actuator arm 306 aor 306 b, which allows for the displacement of actuator bar 332 a,b andswing arm 310 a,b away from stationary member 296 a, 296 b.

Optionally, a cassette mount retaining member 334 can be used to holdcassette mount 298 in a retracted position. In one example, cassettemount retaining member 298 may comprise a pawl, which is pushed aside bycrossmember 304 (or alternatively another element attached to cassettemount 298, flange 300, rail 302 or shaft/pinion 318) when handle 308 ispulled fully into a retracted position (see FIG. 56). When crossmember304 reaches a pawl recess 336, it drops down to engage crossmember 304,and holds cassette mount 298 in its retracted position. In an additionalor alternative embodiment, handle 308 may include a movable plungerelement (substituting for handle post 338—See FIG. 57, 59) that canengage or penetrate a hole or recess (not shown) in a forward flange 340of stationary frame 294. Optionally, the plunger can be spring-loaded toautomatically engage the forward flange when handle 308 is released by auser.

As applied to hemodialysis enclosure 254 (see FIG. 23), cassette seatingapparatus 292 can be mounted to a ceiling of the interior of enclosure254, as shown in FIGS. 45 and 46. This is in a position opposite thereceptacle assemblies 266, 268, 270 (in this case manifold adaptors).Cassette assembly 226 can be seen installed in a cassette seatingapparatus 292 by means of a cassette assembly frame plate 513, forexample, as shown in FIGS. 21 and 46. In FIGS. 30 and 31, cassetteassembly ports 240 are shown to be directly adjacent correspondingreceptacle ports on receptacle assemblies, and disengage completely fromthem as the handle 308 is placed in a retracted position (FIG. 30).

Pneumatic Pump System Using Binary Valves

FIG. 60 is a schematic view showing an embodiment of a pressureactuation system 14000 for a positive displacement diaphragm pump (‘podpump’) 234, such as that shown in FIG. 20. In this example, air pressureis used as a control fluid (e.g., such that the pump is pneumaticallydriven). Other fluids (e.g., water or water-based solutions) may also beused as control fluids in other embodiments.

In FIG. 60, the pressure actuation system 14000 alternately providespositive and negative gas pressure in the actuation chamber 14020 of thepod pump 23 a. The pneumatic actuation system 14000 includes anactuation-chamber pressure transducer 14020, a positive-supply valveLP1, a negative-supply valve N1, a positive-pressure gas source LPOS, anegative-pressure gas source NEG, a positive-pressure source pressuretransducer (not shown), a negative-pressure source pressure transducer(not shown), as well as an electronic controller 14035. The electroniccontroller receives pressure data from pressure sensor 14020 andcontrols valves N1, LP1 to control operation of pump 23 a. These twovalves are controlled by an electronic controller 14035. (Alternatively,a single three-way valve may be used in lieu of the two separate valvesLP1, N1.) In some cases, the positive-supply valve LP1 and thenegative-supply valve N1 are binary on-off valves that are either fullyopen or fully closed.

The positive-pressure source LPOS provides to the actuation chamber14020 positively pressurized control gas to urge the diaphragm 14025towards a position to minimize the pumping chamber 14027 volume (i.e.,the position where the diaphragm is against the rigid pumping-chamberwall). The negative-pressure source NEG provides to the actuationchamber 14020 negatively pressurized control gas to urge the diaphragm14025 in the opposite direction, towards a position to maximize thepumping chamber 14027 volume (i.e., the position where the diaphragm isagainst the rigid actuation-chamber wall).

The controller 14035 may also receive pressure information from threeother pressure transducers: an actuation-chamber pressure transducer14020, a transducer on LPOS and a transducer on NEG. As their namessuggest, these transducers respectively measure the pressure in theactuation chamber 14020, the positive-pressure source LPOS, and thenegative-pressure source NEG. The controller 14035 monitors the pressurein the two sources LPOS, NEG to ensure they are properly pressurized(either positively or negatively). A compressor-type pump or pumps maybe used to maintain the desired pressures in reservoirs that comprisesources for LPOS, NEG.

In one embodiment, the pressure provided by the positive-pressurereservoir LPOS is under normal conditions of sufficient magnitude tourge the diaphragm 14025 all the way against the rigid pumping chamberwall. Similarly, the negative pressure (i.e., the vacuum) provided bythe negative-pressure source NEG is preferably of sufficient magnitude,under normal conditions, to urge the diaphragm all the way against therigid actuation chamber wall. In preferred embodiments, however, thepositive and negative pressures provided by the sources LPOS, NEG arekept within safe enough limits to avoid excessively high liquidpressures that could harm a patient to which the pumping system may beconnected.

The controller 14035 monitors the pressure information from theactuation-chamber-pressure transducer 196 and, based on this informationand possibly a timer, controls the valving mechanism (valves LP1, N1) tourge the diaphragm 14025 all the way to itsminimum-pumping-chamber-volume position, followed by a switch ofpressure to pull the diaphragm 14025 all the way back to itsmaximum-pumping-chamber-volume position.

The pressure actuation system comprises a pressure distributionmanifold, which may contain the actuation-chamber pressure transducer14020, the transducer for LPOS source, the transducer for NEG source,the positive-supply valve LP1, the negative-supply valve N1. Thecontroller 14035 may be mounted on the manifold, and thepositive-pressure gas source LPOS, and the negative-pressure gas sourceNEG may include conduits running through the manifold. The manifold maybe constructed to fit entirely or mostly in the hemodialysis housingrecess 258 (see, e.g. FIGS. 44, 48). In this arrangement, the componentsthat come into contact with blood or dialysate (namely, pod pump 23 a,the inlet valve 192 and the outlet valve 193) may be located in aninsulated enclosure 254 or a front panel 248 (see FIG. 23) so that thepump, valves and interconnecting liquid paths can be more easilyaccessed and/or disinfected.

Pumping Process with Binary Valves

The process of pumping liquid through the pod pump 23 a can be betterunderstood by referring to FIGS. 61 and 62. Referring now to FIG. 61,the target pressure 14050 and the actual pressure 14055 measured by apressure sensor 196 (FIG. 60) are plotted against time for one deliverstroke and one fill stroke. A deliver stroke comprises using positivepressure from the LPOS source to drive the diaphragm 14025 from one sideof the pump pod 23 a to the other and expelling the liquid in thepumping chamber 14027. A fill stroke by contrast, uses sub-atmosphericpressure from the NEG source to pull the diaphragm 14025 back across thepod pump 23 a and fill the pod pump with liquid. In some examples, thefill stroke is completed by connecting the actuation chamber 14020 toatmosphere, allowing liquid pressure in the system to drive thediaphragm across the pod pump chamber.

In a binary valve-driven pump 14000, the deliver and fill pump strokescomprise multiple charge cycles which produce the jagged pressure trace14050 of FIGS. 61 and 62. A detail of the start of a deliver stroke isshown in FIG. 62, in which during liquid movement, the actual pressure14055 rises when the valve LP1 is open and falls when the valve LP1 isclosed. In the deliver stroke, the movement of liquid from the pumpingchamber 14027 decreases the volume of the pumping chamber; and becausethe total volume of the pod pump is fixed, this increases the volume ofthe actuation chamber 14020. The increased volume of the actuationchamber results in a reduction of the pressure in the actuation chamberif the pneumatic valve LP1 is closed. A charge cycle comprises thepressure rise resulting from an open valve and the pressure decay whenthe valve is closed. The length of the charge cycle may vary as shown inFIG. 62, where 3 complete charge cycles are shown and each has adifferent duration. FIG. 62 plots the details of a delivery stroke, inwhich positive pressure is applied. Referring now the fill stroke toFIG. 61, the pressure trace 14055 has a similar jagged pattern. However,during the fill stroke, the pressure drops quickly when the N1 valve isopen, exposing the actuation chamber to the NEG source, and recoversmore slowly toward atmospheric pressure when the N1 valve is closed.Once again the charge cycle comprises a rapid increase in the magnitudeof the actuation chamber pressure and a slower pressure decay towardatmospheric pressure when the N1 valve is closed.

Where in previous applications and disclosures, continuously variablevalves were used to control diaphragm pumps, binary valves are hereindescribed that are either fully open or fully closed and not designed tobe partially open. Binary valves and the associated control electronicsare generally less expensive than variable-opening valves. In addition,binary valves may require less functional checks/monitoring, and may beless sensitive to the presence of debris in the pneumatic passagesleading to or away from them. The inherent digital or on/offfunctionality of the binary valves require unique control algorithms forpressure control and detection of end-of-stroke, and flowpathocclusions.

The controller 14035 controls the valves N1 and LP1 based on receivedsignals from the pressure sensor or transducer 196 according to a numberof algorithms that may run sequentially or simultaneously. These controlalgorithms are unique to binary valves due to their inherent digital oron/off functionality. The control algorithms include algorithms tocontrol the fluid flow rate through the pump, to control the pressureinside the actuation chamber 14020, to detect an end-of-stroke (EOS)condition, to detect a full occlusion of the inlet line, to detect afull occlusion of the outlet line, to detect partial occlusions, and tomeasure an access metric (an indication of the quality of the blood flowobtained from a patient's venous or fistula access).

The controller 14035 computes information about liquid flow through thepump based on the pressure signal from sensor 196 when the valves N1,LP1 are closed. The controller 14035 uses the received pressure data tocontrol the actuation chamber pressure, detect EOS, occlusions, partialocclusions and determine the access metric.

Pressure Control Description

The flow rate through a pneumatically actuated diaphragm pump such aspod pump 23 a is controlled by setting a target pressure for theactuation chamber 14020. The pod controller 14035 then controls pressurein the actuation chamber 14020 as measured by a pressure sensor 196fluidically connected to the actuation chamber 14020 by controlling avalve N1, LP1, that fluidically connects a pressure source to theactuation chamber of the pump. In an exemplary control algorithm, thecontroller averages the pressure data from pressure sensor 196, whilethe binary valve N1, LP1 is closed, and opens the valve N1, LP1 when theaccumulated averaged pressure approaches or equals the target pressure.In one example the controller 14035 closes the valve N1, LP1 when themagnitude of the pressure data equals or exceeds the target pressure. Inone example, the controller 14035 closes the valve N1, LP1 when themagnitude of the pressure data equals or exceeds the target pressureminus a predetermined constant value. In another example, thepredetermined value, rather than being constant, varies with the strokedirection and the duration or stage of the stroke. In another example,the controller 14035 integrates the difference between the magnitude ofthe measured pressure and target pressure and opens the valve N1 LP1when an integrated difference approaches or equals zero.

Fluid flow through the pump is controlled by the magnitude of negativepressure applied to the actuation chamber to fill the pumping chamberwith liquid and the magnitude of the positive pressure applied to theactuation chamber to deliver liquid from the pumping chamber. In someexamples, the pod pump controller 14035 is programmed to receive orcompute a desired flow rate and/or the maximum displaced volume of thepod pump 23 a. The controller 14035 may set initial target pressures forfill and deliver strokes. The controller controls the pressure in theactuation chamber to reach or approach a target pressure. The controllermonitors the time to complete a stroke and determine the actual flowrate by dividing the displaced volume by the stroke completion time. Thecontroller 14035 may change the target pressure based on a differencebetween the most recent actual flow rate and the desired flow rate. Forexample, the controller 14035 may increase the target pressure if themeasured actual flow rate was below the desired flow rate. In anotherexample, the controller may decrease the target pressure if the measuredactual flow rate is above the desired flow rate. The controller 14035may modify the deliver stroke independently of the fill stroke. In oneexample controller 14035 may use a feedback loop that modifies thedeliver target pressure based on the measured flow rate during deliverstrokes in order to achieve a desired flow rate. In another example thefeedback loop modifies the negative fill target pressure to be based onthe measured flow rate during fill strokes in order to achieve a desiredfill rate.

In previous disclosures, a chamber connected by a binary valve to apressure source has been controlled based on limits about the targetpressure. The controller would connect the pressure source to thechamber by opening a valve between them when the magnitude of themeasured pressure in the chamber was some predetermined amount below thetarget pressure magnitude. The controller would then close the valvewhen the magnitude of the measured pressure in the chamber was a secondpredetermined value above the target pressure magnitude. In some cases,applying this limit approach to pneumatic diaphragm pumps produces anaverage chamber pressure magnitude that is less than the target pressuremagnitude. In some cases, opening the valve produces a very rapidincrease in the magnitude of the pressure in the chamber, while the dropin the pressure magnitude due to liquid flowing in or out of the pumpingchamber was much slower. This mismatch in rate of pressure changesbiases the magnitude of the time-averaged pressure below the targetpressure magnitude. In cases in which the liquid flow into or out of thepump varies with time, the offset between the average pressure and thetarget pressure can also change with time, making it difficult tocontinuously correct for the mismatch in rate of pressure changes.

The pressure in the actuation chamber may be controlled by comparing themeasured pressure to a target pressure. The controller opens and closesa pneumatic valve that connects the actuation chamber to a pressuresource or reservoir. The controller may open and close valve LP1 duringthe delivery stroke to maintain the pressure in the actuation chamber14030 near the delivery target pressure 14052. The controller 14035opens and closes valve N1 during the fill stroke to maintain thepressure in the actuation chamber 14030 near the fill target pressure14054. In one example, the controller closes pneumatic valve when themagnitude of the measured pressure exceeds the target pressure, andreopens the pneumatic valve when the averaged measured pressure in theactuation chamber approaches or equals the target pressure.

In the algorithm shown in FIGS. 63 and 64, referencing FIG. 62 anddescribed below, the controller 14035 controls the valves N1, LP1 tohold the average pressure in the actuation chamber 14020 at the targetpressure by maintaining the average pressure in the actuation chamber atthe target pressure while the valves N1, LP1 are closed. Referring nowto pressure control algorithm 14100 in FIG. 63 and referencing FIG. 60,a pump controller (that may be separate or distinct from controller14035 in FIG. 60) selects the stroke direction 14105 and targetpressure, Fill and PTF (Pressure-Target-Fill) or Deliver and PTD(Pressure-Target-Deliver). If a Fill stroke is selected, then in 14110the controller 14035 opens the valve fluidically connecting the NEGsource or reservoir to the actuation chamber 14020, and monitors thepressure sensor 196 in 14120. At each time step in Block 14130, thecontroller evaluates whether the pressure magnitude is greater than themagnitude of the target pressure, and if not leaves the valve open. Inblock 14140, once the magnitude of the measured pressure is equal to orgreater than the target pressure, the N1 valve is closed. In block14150, the difference between the measured pressure P and the targetpressure TTF is summed at each time step. In block 14160, theend-of-stroke function or algorithm checks for an end-of-stroke anddirects the controller logic to end-of-stroke 14200 if the EOS criteriaare met. Note that the logic in block 14160 may be positioned anywherein the flow chart between 14140 and 14180, or may be a separate functionfrom the pressure control algorithm 14100. In block 14170 the summedpressure difference is compared to zero. If the summed pressuredifference is greater than zero, controller logic returns to 14150 foran additional time step. In the case in which the sum of pressuredifferences is equal to or less than zero the controller logic zeros thepressure difference sum in block 14180 and returns the logic to block14110 where the N1 valve is opened.

A single controller can coordinate the timing of pump strokes, thesetting of target pressures, and the operation of the pneumatic controlvalves. Alternatively, the tasks can be divided between two or morecontrollers, for example with a main controller determining the timingof pump strokes and the target pressures, and a sub-controllercontrolling the pneumatic control valves. Referring to FIGS. 63 and 60,if a main controller selects a deliver stroke, it also defines a targetpressure and the sub-controller moves the logic to block 14210 (FIG. 63)in which the LP1 valve is opened. In a series of steps similar to theFill process, the pressure in the actuation chamber 14020 is monitoredby pressure sensor 196 in block 14220. Block 14230 evaluates thepressure against the target pressure and if the measured pressure isequal to or greater than the target pressure, directs the logic to block14240 where the LP1 valve is closed. Referring now to FIG. 60, thechamber pressure 14055 continues to increase after the LP1 valve iscommanded to close at 14051, where the chamber pressure exceeds thetarget pressure. The chamber pressure 14055 may increase to 14052 due tothe delay in the valve closing and due to fluid/thermal dynamics thatmay affect the chamber pressure.

Referring to FIG. 63, in block 14250, the difference between the chamberpressure P and the target pressure PTD is summed for each time step. Thesum of this difference between the chamber pressure P and the targetpressure PTD from point 14052 until the chamber pressure 14055 equalsthe target pressure 14050 is the area 14080 in FIG. 62. The area 14085is the sum of difference between the chamber pressure and the targetpressure when the magnitude of the chamber pressure 14055 is less thanthe magnitude of the target pressure 14050. Referring again to FIG. 63,in block 14260 the EOS algorithm is run and the stroke ended at 14200 ifan EOS is detected.

In block 14270, the sum of pressure difference from block 14250 isevaluated. Block 14270 directs the logic to 14210 where the LP1 valve isreopened, if the sum of the pressure differences is less than or equalto zero. The pressure difference sum is set to zero in block 14280before the logic reaches block 14210, at which point LP1 is opened.Alternatively, the pressure difference sum may be zeroed any time in thelogic after block 14270 and before block 14240

Referring now to FIG. 62, the criteria of block 14270 can be graphicallyrepresented as the instance in which the area of 14080 is equal to thearea of 14085. The criteria of block 14270 is met when the sum of theactual pressure 14055 less the target pressure 14050 (for actualpressures greater than the target pressure) is equal to the sum of thetarget pressure 14050 less the chamber pressure 14055 (for chamberpressures less than the target pressure). Alternatively, the criteria of14270 is met when the sum of [the average pressure magnitude less thetarget pressure magnitude] is equal to or less than zero.

In one example, blocks 14130 & 14230, the chamber pressure P is comparedto predetermined pressures PD, PF that are different by a pressureoffset from the target pressures PTD, PTF. In some examples, in order tolimit the overshoot of the pressure, the magnitudes of PD, PF are apredetermined value less than the magnitude of the target pressures PTD,PTF. Referring now to FIG. 62, if PD is less than the Target pressure(14050D), then the signal to the valve LP1 in FIG. 60 will be sentsooner and the peak pressure at 14052 will be lower. In one example, themagnitude of the pressure offset is different for the fill stroke andthe deliver stroke because the mean pressures for fill stroke anddeliver stroke are different.

As the delay in the valve actuation is a fixed value and the pressureovershoot is inversely proportional the volume of the actuation chamber(which changes during the stroke), the overshoot can also vary, as canbe seen in FIG. 61. In general, the overshoot is largest at the start ofthe deliver stroke 14060 and end of the fill stroke 14075 when theactuation chamber 14020 volume has the smallest volume. The offset forthe fill and deliver strokes may vary during the stroke. In one example,the offset magnitude is largest at the beginning of the deliver strokeand is reduced with each charge cycle until the offset reaches a minimumvalue. In the same or another example, the offset magnitude is smallestat the beginning of the fill stroke and increases with each charge cycleuntil the offset reaches a maximum value. The offset values may varywith time, number of charge cycles, valve openings or the summeddifferential pressures when the valves are closed during the stroke.

Another example of the pressure control algorithm 14300 is presentedFIG. 64. The algorithm 14300 is similar to algorithm 14100 except forelements 14350, 14370, 14380, 14450, 14470 and 14480, in which theaveraged pressure replaces the difference between the measured pressureand the target pressure. In blocks 14350 and 14450, the pressure sensor196 measurements are averaged while the valves N1, LP1 are closed. InBlock 14370 and 14470, if the averaged pressure, PAVG is equal to thetarget pressure within some predetermined margin, the logic proceeds toblocks 1410, 14210 respectively to open the valve N1, LP1 after zeroingout the average pressure.

Detecting End-of-Stroke

The accurate or reliable determination of flowrates and flow volumesthrough a pump 23 a as pictured in FIG. 60 depends on an accurate orreliable algorithm to determine end-of-stroke (EOS). The end-of-strokeoccurs when the diaphragm 14025 has moved across the cavity of the pumpbody and reached one of the walls of the pump body. The controller 14035detects the condition of the chamber against the wall by observing thatthe chamber pressure magnitude, as measured by the pressure sensor 196,does not drop when the valve N1, LP1 is closed. The chamber pressuredoes not drop because the diaphragm 14025 is against the wall of thechamber and cannot move, and therefore cannot change the volume of theactuation chamber 14020.

The EOS detection algorithm detects an end-of-stroke condition based onvalve conditions, chamber pressure and rate of change of the chamberpressure. The algorithm detects an EOS condition for a pneumaticallydriven diaphragm pump, where the pneumatic pressure is controlled by apneumatic valve connecting the pump to a pressure reservoir, a pressuresensor measuring the pneumatic pressure applied to the pump and acontroller in communication with the pump and pneumatic valve. In oneexample, the EOS detection is based on the number of charge cyclesexecuted by the pneumatic valve and the rate of pressure change whilethe pneumatic valve is closed. In another example, the EOS is declaredwhen a predetermined number of charge cycles have occurred and the rateof pressure magnitude change is less than a predetermined rate. Inanother example, the EOS detection is declared when a predeterminednumber of charge cycles have occurred, the pressure is within apredetermined range and the rate of pressure magnitude change is lessthan a predetermined rate.

Referring now to FIG. 60, the controller 14035 changes stroke directionfrom deliver to fill or fill to deliver after detecting an end-of-stroke(EOS). The end of stroke algorithm is described schematically in FIG. 65and can be understood with reference to FIG. 61. The EOS algorithm 14300runs as part of the pressure control algorithm 14100, in blocks 14160and 14260, or the EOS algorithm may run in parallel. Block 14310monitors the pressure in the actuation chamber as sensed by pressuresensor 196 (FIG. 60). In block, 14320, the number of charge cycles thathave occurred during the current stroke are compared to a predeterminednumber. If more than the predetermined number of charge cycles haveoccurred, then in block 14330 the minimum rate of pressure magnitudechange (dP/dt) is compared to a predetermined rate (dPEOS). If theminimum rate of change is less than the predetermined rate, then inblock 14340 the difference between the current pressure P and the targetpressure PT is evaluated. If the difference is smaller than apredetermined difference DP, an EOS is declared and the controllerchanges pump strokes, target pressure, and switches the state of thehydraulic valves 192, 193 (valves which in the presently describeddialysis system may be diaphragm valves that can also be actuated bypressures delivered by the manifold and controlled by the controller).If the difference between the chamber pressure and the target pressureis greater than the predetermined difference, then the controller 14035declares an occlusion.

Still referring to FIG. 65, in block 14330, dP/dt is the minimum rate ofchange of the magnitude of the pressure in the actuation chamber. Insome examples, the minimum rate of change is only determined while thepneumatic valves, N1, LP1 are closed. In some examples, the minimum rateof change of pressure magnitude is derived from a low pass filtering ofthe pressure values. In another example, the rate of change of pressuremagnitude is itself is low-pass-filtered before being compared to thepredetermined rate of pressure change (dPEOS).

Occlusion Detection

Referring now to FIG. 60, the controller 14035 can be configured todetect occlusions in the flow to and from pump 23 a. The user interfacemay signal an alert or an alarm that an intake or outlet line isoccluded. In one example, a user can be instructed to inspect the bloodlines 203 and 204 for kinks, compressions or other obstructing elements.An occlusion detection algorithm can be considered a safety feature thatprevents thrombosis in the blood circuit, or can identify a problem withfluid flow in the water or dialysate circuits.

Occlusions in the pump inlet and outlet lines are detected by thecontroller 14035 based on information received from the pressure sensor196, while actuation chamber 14020 is isolated from pressure reservoirsNEG, LPOS. The pressure sensor 196 measures the pressure in theactuation chamber. The controller 14035 detects occlusions in the inletline during fill strokes and occlusions in the outlet line duringdeliver strokes. The controller 14035 sums the change in pressure thatoccurs in the actuation chamber while the valve N1, LP1 is closed. Thecontroller 14035 determines the presence of an occlusion by comparingthe sum of the pressure changes over all the charge-cycles during asingle pump stroke to sums of pressure difference during previousstrokes and to an predetermined value. The controller 14035 may alsobase the detection of an occlusion on the number of charge cyclescompleted before an end-of-stroke is detected and/or the differencebetween the actuation chamber pressure and the target pressure.

Referring now to FIG. 66, where the occlusion algorithm 14400 ispresented as a flow chart starting at step 14410 in which either a fillstroke or deliver stroke is initiated by setting a target pressure andthen opening a valve N1, LP1 (FIG. 60) in step 14415. The valve N1, LP1is closed in step 14420. In step 14425 the controller sums the pressurechange (dPSUM) while the pneumatic valves N1, LP1 are closed. The sum ofpressure changes (dPSUM) is summed over the entire stroke includingmultiple charge cycles 14427. In one example, the controller 14035determines the pressure change from the previous time step to thecurrent time step: Pi-1-Pi and adds this pressure change to the currentsum of pressure changes for each time step that the pneumatic valve N1,LP1 is closed. In one example, the controller determines the pressurechange between the time the valve N1, LP1 closes and then reopens andthen adds this pressure change to the sum of pressure changes (dPSUM)that includes all the pressure changes since the stroke started at step14410.

Continuing to refer to FIG. 66, the occlusion algorithm 14400 checks foran End-of-Stroke condition in step 14430 after updating the sum ofpressure change (dPSUM) in step 14425. If an EOS is not detected, thenthe controller 14035 in step 14435 checks to see if the charge cycle iscomplete and it is time to reopen the valve. The end of charge cyclestep 14435 can be done based on one or more parameters, including (butnot limited to) the current pressure, the average pressure during thecurrent charge cycle, or the integrand of the pressure differencebetween the target pressure and chamber pressure during the currentcharge cycle. If step 14435 determines the charge cycle is not complete,then sum of pressure changes is updated for the next time step in step14435. If the charge cycle is complete, then the pneumatic valve N1, LP1is reopened in step 14415.

When an end-of-stroke is determined in step 14430, the occlusionalgorithm 14400 proceeds to multiple independent occlusion tests insteps 14440, 14450, 14455, 14460. Step 14440 directs the logic for lowsensitivity to step 14450 and high sensitivity to step 14445. In oneexample, step 14440 selects low sensitivity for short or partial strokesof the blood pump due to the variability of short stroke in the bloodpump. In short strokes, the diaphragm is not driven against the insidewall of the pod pump. Instead, the delivery stroke is shortened. In somemedical applications, the short deliver stroke may be beneficial inreducing damage to blood cells between the diaphragm 14025 and the wallsof the pod pump 23 a. The short strokes have greater variability; and toavoid false occlusion detections, the low sensitivity occlusion test instep 14450 may be preferred. In one example, step 14440 directs thelogic to step 14445 for all non-short stroke operations.

Continuing to refer to FIG. 66 where the occlusion algorithm 14400, instep 14445, compares the sum of pressure differences during justcompleted stroke (dPSUM) to the sum of pressure difference for the lastgood stroke in the same direction (dPGOOD). In one example, an occlusionis detected when two consecutive strokes in the same direction have adPSUM that is less than 30% of the last good stroke (dPsum). In moregeneral terms, an occlusion is detected when one stroke has a dPSUM thatis less than a predetermined fraction of the last good stroke (dPsum).In one example, an occlusion is detected when more than two strokes havea dPSUM that is less than a predetermined faction of the last goodstroke (dPsum). If an occlusion is detected, the logic moves to step14470 where an occlusion alert or alarm is sent to the user interface(UI), and in one example the pump may be stopped. In some embodiments,the UI indicates which pump and where the inlet or the outlet line isoccluded. If an occlusion is not detected in 14445, the logic moves tostep 14455.

FIG. 66 outlines the occlusion algorithm 14400 includes, in lowsensitivity step 14450, a comparison of the sum of pressure differencesduring just-completed stroke (dPSUM) to the sum of pressure differencefor the last good stroke in the same direction (dPGOOD). In one example,an occlusion is detected when three consecutive strokes in the samedirection have a dPSUM that is less than 10% of the last good stroke(dPsum). In one example, an occlusion is detected when one stroke has adPSUM that is less than a second predetermined fraction of the last goodstroke (dPsum). Alternatively, an occlusion is detected when more thanthree strokes have a dPSUM that is less than a predetermined faction ofthe last good stroke (dPsum). If an occlusion is detected the logicmoves to step 14470 where an occlusion alert or alarm is sent to theuser interface (UI) and in one example the pump is stopped. In anembodiment, the UI indicates which pump and where the inlet or theoutlet line is occluded. If an occlusion is not detected in 14450, thelogic moves to step 14455.

In step 14455, the controller 14035 detects an occlusion if in one ormore consecutive strokes in the same direction either of the followingconditions occur: less than a predetermined number of charge cyclesoccur, or the sum of the pressure changes (dPsum) is less than apredetermined limit (dPsum_limit). In one example, an occlusion isdetected if either condition occurs in 3 consecutive strokes in the samedirection. In another example an occlusion occurs if either conditionsoccurs in 2 consecutive cycles. In another example, the predeterminednumber of charge cycles is 5. In another example, predetermined numberof charge cycles is half of the number of charge cycles in a typicalstroke. If an occlusion is detected the logic moves to step 14470 inwhich an occlusion alert or alarm is sent to the user interface (UI). Inone exemplary response, the pump is stopped. The controller may senddata to the UI to indicate which pump is affected and whether theocclusion occurred in the inlet or the outlet line. If an occlusion isnot detected in 14455, the logic moves to step 14460.

In step 14460, the controller 14035 detects an occlusion if themagnitude of the pressure in the actuation chamber 14020 issignificantly greater than the target pressure for a predeterminedperiod of time. In one example, step 14460 detects an occlusion if themagnitude of the pressure in the actuation chamber 14040 is larger thanthe target pressure magnitude by more than 60 mmHg for a predeterminedperiod of time. In another example, the predetermined period of time instep 14460 is 25% of the stroke duration, the stroke duration being thetime from the start of the stroke to EOS detection.

Partial Occlusion Detection

A partial occlusions may limit the flow rate, but not block the flow inliquid lines. The functions of the hemodialysis machine may be modifiedand/or the messages to the user may be changed depending on whether apartial occlusion or a full occlusion is detected. The controllerdetects a partial occlusion based on the flow rate of a recent strokeand stroke target pressure of that recent stroke. The pump controllervaries the target pressure to achieve a desired flow rate and increasesthe target pressure for the next stroke, if the last stroke flow ratewas below the desired flow rate. There are maximum target pressures fora given pump, in which the maximum pressure may be a function of thepressure reservoir pressure and/or the use of the given pump. In anexample, a partial occlusion can be declared if the recent flowratethrough the pump does not achieve the desired flow rate despite settingthe target pressure for that recent stroke to the maximum value. Inanother example, a partial occlusion can be declared when the flowrateof a recent stroke is less than 75% of the desired flowrate despite thetarget pressure for the recent stroke having been set to the maximumvalue. In a hemodialysis system, the partial occlusion detection featurecan be applied to the blood pumps to determine if there is a problemwith an individual's vascular access or with the positioning of a set ofblood lines.

Blood Flow Metrics

In an embodiment, the controller may be programmed to provide a user ofan extracorporeal or hemodialysis system an indication of blood flowmetrics (the quality or rate of flow of blood from a venous access orarterio-venous fistula) during the course of each pump fill-stroke. Forexample, a flow metric value may be transmitted to a graphical userinterface, providing the user with an ongoing indication of the qualityor adequacy of blood flow in the blood line during therapy. A userinterface (such as, e.g. an electronic tablet) may provide the user withraw flow metric data. In another embodiment, the flow metric may beproportionally scaled to a range of 1 to 5, with the value ‘5’representing, for example, excellent flow, a value ‘3’ representingmarginal flow, and a value ‘1’ occluded flow. Thus a specified range offlow metric values may be mapped into each of a set value of ‘1’ to ‘5,’simplifying a user's interpretation of the adequacy of blood flow in theblood line. In other embodiments, the flow metric may be displayed tothe user graphically, such as a moving or expanding bar graph, a dialgauge, or a set of colored lights, for example.

In a preferred embodiment, a marginal or sub-optimal flow metric maycause the controller to alert the user, so that the user may attempt toimprove blood flow in the blood line (e.g., reposition the line,straighten out the line, adjust the vascular access cannula, etc.). Thecontroller may be programmed initiate a procedure to pause or stop thedialysate pump that includes signaling the user and providing sufficientpassage of time before the pausing or stopping of a dialysate pump toallow the user to correct the condition. The user may be alerted to thelow-flow condition during a fill-stroke, so that a timely adjustment bythe user allows the flow metric to be restored to an acceptable valuebefore the end of the fill-stroke. Alternatively, the controller may beprogrammed to allow sub-optimal flow metric values for two or three (ormore) consecutive fill-strokes before commanding the dialysate pump tostop. Thus a timely correction of the low-flow condition by the user mayforestall the interruption of dialysate pumping operations, and possiblyinterruption of therapy. In an example, the controller may be programmedto pause or stop the dialysate pump if the flow metric remains below 150(e.g., as dP/dt in mm Hg/sec.) for three consecutive fill-strokes, andmay be programmed not to re-start the dialysate pump until the flowmetric exceeds 200 for five consecutive blood pump strokes. In some ofthese embodiments, the controller allows the blood pump to continue tooperate while the dialysate pump has been suspended, so that the userhas an opportunity to restore a blood flow condition that allows thedialysate pump to be re-started, thus avoiding early termination oftherapy.

Referring now to FIGS. 60 and 62, the controller 14035 may determine theflow metric during a fill stroke based on the actuation chamber pressurewhile the pneumatic valve N1 is closed. The actuation chamber pressureis measured by the pressure sensor 196 which is in communication withthe controller 14035. In one example, the controller 14035 may determinethe flow metric based on the rate of change of the signal from thepressure sensor 196 while the valve N1 is closed. In another example thecontroller 14035 may determine the flow metric based on the minimum rateof change of the actuation pressure during the stroke while the valve N1is closed (i.e., the lowest or near-lowest rate of pressure changedetected by the controller). In another example, the controller 14035may determine the flow metric based on the minimum rate of change of theactuation pressure during the stroke, excluding the charge cycle thatproduced an end-of-stroke signal. In one example, the rate of change inthe actuation pressure is determined during each charge cycle using alow-pass-filter and the minimum values of the rate of change for eachcharge cycle are low-pass-filtered over a stroke to determine the flowmetric.

FIG. 67, illustrates the flow metric algorithm 14500 as a flow chartstarting with “begin a fill stroke” with a blood pump (23 a in FIG. 60).The upstream valve 192 is opened and the downstream valve 193 is closed.The fill stroke continues by opening pneumatic valve N1 in step 14515and closing valve N1 in step 14520 to create a desired negative or belowambient pressure in the actuation chamber 14020 of the blood pump 23 a.The negative pressure in the actuation chamber 14020 draws blood fromthe access site through the tubing 203 into the pumping chamber of bloodpump 23 a. The magnitude of the negative pressure in the actuationchamber 14020 decreases as the filling pump chamber expands andcompresses the gas in the actuation chamber 14020. This reduction in themagnitude of the negative pressure is sensed by pressure sensor 196 andcommunicated to controller 14035 in step 14525 (FIG. 67). The controlleranalyzes the data, and (optionally) using a low-pass filter (LPF)function determines the rate of change of pressure (dP/dt) in theactuation chamber in step 14530. If the end of the charge cycle hasoccurred, step 14535 directs the logic to step 14540 at whichend-of-stroke (EOS) is determined. If the end of the charge cycle hasnot occurred, then the logic is directed to 14525 in which the pressuresignal continues to be monitored. If an EOS is not detected in step14540, then the controller determines, in step 14545, the smallestmagnitude of dP/dt while the valve N1 was closed. The minimum or lowestdP/dt of the current charge cycle detected by the controller is thenused in the LPF to update the minimum dP/dt for the fill stroke in step14550 and then the valve N1 is reopened to start the next charge cyclein step 14515.

If an EOS is detected in step 14540, then the logic flows to step 14555,at which the pod controller 14035 reports out the minimum dP/dt to acontroller that converts the minimum dP/dt value to a more easilyunderstood indicator that in turn is displayed on the user interface(UI). The UI may be a graphical display unit such as a tablet computer.The indicator is the flow metric of the intake blood line and access. Inan example, the minimum dP/dt values are displayed as a value from 1 to5, where 1 is an occluded access, 3 is a marginal access and 5 is freelyflowing access. Here access means the system of needle or cannula,placement of needle or cannula and flow restrictions at inlet to needleor cannula. In an example, the flow metric is 1 or occluded for minimumdP/dt less than 25 mmHg/s, the flow metric is 2 or poor for a minimumdP/dt between 25 and 50 mmHg/s, the flow metric is 3 or marginal for aminimum dP/dt between 50 and 75 mmHg/s, the flow metric is 4 or good fora minimum dP/dt between 75 and 100 mmHg/s and the flow metric is 5 orexcellent for a minimum dP/dt between 100 and 125 mmHg/s. In addition todisplaying the flow metric on the UI in step 14555, the flow metricalgorithm 14500 in step 14560 evaluates the flow metric and issues analert to the user 14570 if the flow metric remains below a predeterminedvalue for more than a predetermined number of strokes or period of time.In an example, step 14560 indicates an alert in step 14570 if threeconsecutive fill strokes have a dP/dt below a value of 50 mmHg/s. Inthis case the logic moves to a deliver stroke of the blood pump in step14580 regardless the flow metric or minimum dP/dt and then returns tobegin a fill stroke in step 14510.

Interface with Water Purification Device

The hemodialysis device or apparatus (HDD) can be configured to interactand communicate with a water purification device (WPD) that provideswater to the HDD system for mixing dialysate solution and fordisinfecting the HDD before or after a dialysis treatment. In previousdisclosures, (see, e.g., US Patent Application Publication No.US/2016/0058933), a series of messages and data could be exchangedbetween HDD controller(s) and a WPD controller. In a more streamlinedapproach, the types of interactions between the two devices can belimited, instead relying on pre-programmed or autonomous functions ofthe WPD. In one example, the WPD can be a water vaporcompression/distillation apparatus. Alternatively or additionally, otherwater purification devices and methods can be used, such assemi-permeable membrane filtration, reverse-osmosis, ultravioletirradiation, charcoal adsorption, or any combination of these.

An HDD controller can be configured to send a Start signal to the WPD,representing a command to start normal-temperature water production,with the WPD proceeding according its independently programmedprocessor. This is the mode typically used when purified water is to bedelivered to the HDD for dialysate mixing and therapy. The HDDcontroller can also send a Start Hot Water command to the WPD,representing a command to start hot water production according to theWPD's pre-programmed processes. This is the mode typically used toperform a disinfection procedure for the WPD. The line connecting theWPD with the HDD (the water inlet line of the HDD) and the HDD itselfcan be disinfected using operations programmed into one or more HDDcontrollers.

The HDD controller can also command the WPD to enter either a Standbymode or state, or an Idle mode or state. In a water vaporcompression/distillation apparatus, an Idle state may involve pausingpumps or compressors, turning off heaters, closing valves anddeactivating control loops and water level controllers. A Standby modeor state allows the WPD to produce purified water relatively quickly;and optionally in a vapor/distillation system this may include fillingthe purification system with water and heating it to a point at whichpurified water production can begin, control a vent valve to maintain alow pressure vapor temperature target, as well as optionally producingenough water to fill a reservoir, or alternatively sending excess waterit produces to drain. If the WPD is starting from an inactive (Off)state or an Idle state, the HDD controller optionally can be programmedto send the command early enough to allow the WPD to be producing waterby the time the HDD expects to receive water delivery. (In some cases,this may amount to about 2 hours from a cold start or a start from Idlemode, or as little as about 10 minutes from a Standby mode). In mostcases, the HDD controller will command an idling WPD into a Standby modewhen the two systems establish communications, or when one or bothsystems reboot after being powered off. This may not occur if an errorcondition has been flagged.

During water delivery, the HDD controller can send a Stop signal to theWPD, which commands the WPD to enter a Standby state. In this case, theStandby state is an autonomous function of the WPD that keeps waterproduction or purification sufficiently active to be able to deliverwater on command by the HDD within a relatively short time period (e.g.,within about 10 minutes of a Start or Resume command being sent by theHDD to the WPD). Among other operations, this may include filling thepurification system with water and heating it to a point at whichpurified water production can begin quickly.

The HDD controller can also send a Start Disinfect command to the WPD,which is generally scheduled to occur after a dialysis therapy has beenconcluded, or during a time between therapy sessions with the HDD. Inthis case, the WPD enters an automated hot water production mode. In atypical sequence, the HDD first commands the WPD into a water productionmode, followed by a command to a disinfect mode once the WPD signalsthat it has entered the water production mode. Once the water producedby the WPD reaches a specified temperature (e.g. 90 deg. C.), the HDDcontroller is signaled, and the HDD initiates an Inlet Line disinfectionprocedure. The Inlet Line includes a flowpath within the HDD before abranch point connects it to a flowpath to either drain or to the mixingcircuit of the HDD. (Beyond this branch point, the HDD internalflowpaths can be disinfected through programmed circulation of hot wateror chemical disinfectant without any ‘blind ends’). This state alsodisinfects any tubing that connects an output port or line of the WPD toan input port or line of the HDD.

A controller of the HDD can be programmed to disinfect the WPD-HDDconnecting line and flowpath at a pre-determined minimum temperature fora pre-determined minimum amount of time. For example, the disinfecttemperature can be set at 85 deg. C. for a minimum time of 35 minutes.The temperature can be measured by a temperature sensor located at thewater inlet line of the HDD. To reduce the number of temperature sensorsin the HDD system, the inlet water temperature sensor preferably canalso be located in a position in the HDD flowpaths that can monitor thetemperature of disinfection fluid circulating through the HDD flowpathsduring HDD system disinfection. Depending on the distance the incomingwater travels before reaching the temperature sensor, the minimumdisinfection temperature may optionally be adjusted to account for heatloss before the water reaches the sensor.

FIG. 68 shows a schematic illustration of a fluid flowpath for ahemodialysis system described in previous applications. Section Arepresents a blood flow path of the system, section B represents adialysate fluid balancing and dialyzer delivery section, section Crepresents a dialysate storage, heating and ultrafiltration section, andsection D represents a water inlet and dialysate mixing section. Thewater inlet line 400 is configured to connect externally to a watersource. In the current embodiment, the water source comprises a waterpurification device (WPD), such as a water vaporcompression/distillation apparatus. For ease of reference, inlet waterline 400 is meant herein to represent the entire water line connectionbetween the purified water outlet of a WPD and the point 402 at whichthe HDD inlet water line has a valved connection to the internalflowpaths of the HDD. In reality, this inter-device water line maycomprise one or more connectors or valves. But for disinfectionpurposes, the inlet water line 400 can be considered to include theentire inter-device water line.

Although the internal fluid flowpaths of the WPD and of the illustratedHDD can be configured to achieve a thorough and complete disinfectionprocess, disinfection of the inlet water line and/or the inter-deviceline connecting the WPD to the HDD may require special attention. Notethat the inlet water line 400 has a valved connection 402 to theinternal HDD flowpaths, and that this inter-device fluid connection (WPDoutlet line and HDD inlet line) becomes a blind end for purposes ofthorough disinfection—either chemical or thermal. This condition isreflected in the outlet line of the WPD as well. Although the HDDdialysate heater can be used to heat water that can then be pumped byone or more dialysate pumps in a reverse direction through the HDD inletline, through the WPD outlet line, and thence to a drain connection ofthe WPD, it may be more efficient for purified hot water (or watercontaining an appropriate chemical disinfectant) to be produced by theWPD and sent to the HDD in the normal forward direction, with thedisinfecting liquid then being discharged to a drain line 404 of theHDD.

FIG. 69 shows an isolated view of the section D portion of the HDDsystem flowpath. Although a temperature sensor can be located in line400, it would only serve to monitor incoming water temperature. Forpurposes of disinfection, incoming heated water could be directeddirectly to drain 404, but this flowpath would depend on the action of awater pump located in the WPD. On the other hand, a temperature sensor406 can be located in an internal line 408 connected to water pump 410,which can then provide the pumping action needed to move the waterthrough the line 400 and 408. This sensor can also be used to monitorliquid temperature during disinfection of various internal flowpaths inthe HDD system. Heated liquid from section C in FIG. 68 can be directedto flowpaths in section D via water line 408. The inlet linedisinfecting flowpath incorporating water pump 410 in the illustratedsystem of FIG. 69 (see also FIG. 68) can be directed throughconductivity/temperature sensors 412, 414 in the dialysate mixing path,and thence made to bypass the dialysate tank 416 by closing valve 418and opening valve 420, which leads to the drain line 404. Note that inan alternative embodiment, the monitoring of the temperature ofdisinfecting liquid can also be done using existing temperature sensorsalready installed for the purpose of mixing dialysate (i.e. sensors 412or sensors 414), without adding a temperature sensor in the water inletline 400 or 408. In all of these cases, either actively managed valvesor passive check valves ensure that the disinfecting liquid is beingdirected to the drain line 404.

In an embodiment, and as shown in FIG. 70, initiation of a disinfectionprocedure may first involve having the HDD command 450 the WPD to beginnormal water production. Following this, the HDD initiates 452 thepriming of its flowpaths with water from the WPD. The HDD then commands454 the WPD to produce water heated to the required disinfectiontemperature. Optionally, the temperature at which the WPD producesheated water is higher than the minimum disinfection temperaturespecified for the line interconnecting the WPD and HDD. This is toaccount for heat losses of the water as it travels though theinterconnecting line. For example, if the minimum disinfect temperatureis 85 degrees C., then the WPD may be programmed to produce water at 90degrees C. at its outlet. Optionally, the HDD may be programmed toinitiate 456 its own hot water production using its internal heater(e.g. heater 411 shown in FIG. 68). This prepares the HDD to perform itsown disinfection after the inter-device line 400 has been disinfected,and helps to maintain a high ambient temperature in the HDD housing tolimit heat losses during disinfection of the inter-device line 400. Onceboth the HDD and WPD have heated their respective fluid flowpaths to thespecified temperatures, the HDD controller may then command the WPD tobegin delivering 458 heated water from its product outlet line to theinter-device line (inlet line 400) connecting the WPD to the HDD.

The water disinfect temperature may vary during the disinfection period.Optionally, a controller of the HDD can be programmed to track theamount of time during which the measured temperature meets or exceedsthe minimum disinfect temperature programmed into the controller.

As shown in FIG. 71, optionally before initiating a disinfection counterfor the inter-device line 400, the HDD controller begins controlling aninternal HDD pump and associated valves to circulate 460 incoming heatedwater from the WPD for a pre-determined period of time to fill thedisinfecting flowpath fully with heated water. In addition to theinter-device line, in one example this flowpath may include the flowpathwithin the HDD that directs the disinfecting water through the waterpump 410 in the mixing circuit, through a line that leads to thedialysate tank 416 but is diverted to drain 404 by one or more valves418, 420. (See, e.g., FIG. 69). In one example, the HDD controllerdirects heated water from the WPD to the HDD drain for approximately 2minutes before the inter-device line disinfection counter is started.

The HDD controller may be programmed to include a pre-determined minimumdisinfection temperature (e.g., 78 deg. C.). Once this temperature isdetected by a temperature sensor (e.g., sensor 406, or sensor 412 or414), the controller initiates a disinfection timer 462. If this minimumdisinfect temperature is maintained 464 for a pre-determined minimumdisinfect time (e.g., 35 minutes), then the controller may declaredisinfection of the inter-device line 400 to be complete. The disinfecttimer is updated 464 as long as the temperature detected is at or abovethe minimum disinfect temperature.

Optionally, the controller may be programmed to include a timer 466 thataccumulates an amount of time at which the temperature detected is lessthan the minimum disinfect temperature but greater than or equal to apre-determined low-temperature threshold value (e.g., 70 deg. C.). If apre-determined low temperature timeout value is reached (e.g., 10minutes to timeout the disinfection cycle), then the controller maysignal an alarm to the user interface and command the WPD to suspendwater production 468. Optionally, the controller may also be programmedto signal an alarm and command the WPD to suspend water production 468if the detected temperature is less than a pre-determinedlow-temperature threshold value (e.g., 70 deg. C.).

If the inter-device line 400 disinfection is successful 470, then theHDD controller can close the inlet water line valve 402, command the WPDto begin its disinfection procedure, and initiate the HDD disinfectionprocedure. If the inter-device line 400 disinfection fails, the user isnotified and the WPD is commanded to suspend water production 468. TheHDD controller under these circumstances optionally initiates are-priming procedure of its flowpaths, and resets the disinfectiontimers at 472. The HDD controller then can await a user input 474 toeither re-attempt the disinfection procedure, or not. If not, the HDDoptionally can initiate a call for service 476. The controller mayprovide the appropriate instructions to a user on the user interface, orit may be configured to automatically send the appropriate messages to aremote server and service center via an internet communication link.

The HDD controller may command the WPD to a Flush mode, in which sourcewater flows into the system and through any filters therein. This iscommonly performed after a filter replacement. If a filter replacementis indicated (e.g., a carbon filter), the HDD controller may firstcommand the WPD into an Idle state, followed by an alert to a user on agraphical user interface that the WPD is ready to have its filterreplaced. Once the user indicates completion of this task, the HDD maythen command the WPD to a Standby state, followed by a Flush mode. TheHDD commands a return to the Standby state at the completion of thistask, so that a water production state can be quickly initiated at thestart of therapy. The Flush mode may also be commanded prior to fluidsampling in order to ensure a more reliable indication of the quality ofthe filters. It may also be commanded if the WPD system has been in anIdle or Standby state for more than a pre-determined period of time.

Status messages may be sent between a Water Layer of the HDD systemcontroller architecture and a Therapy Layer of the HDD system controllerarchitecture. Example messages that the Water Layer can receive from theWPD may include:

-   -   The current operational state of the WPD    -   The identification code or identifier of the current WPD    -   The date that the WPD filter was installed    -   Whether the filter needs to be replaced    -   Whether communication with the WPD has been lost    -   Whether the WPD indicates an operational error    -   Whether the WPD indicates a failsafe error    -   The time since the WPD was last disinfected    -   Whether the WPD needs to be disinfected    -   The software version installed on the WPD system controller

Status messages regarding the operational state of the WPD may includeone or more of the following:

-   -   WPD active (independent of HDD); initiation of communications        link between HDD and WPD causes the HDD to command the WPD to        Standby state.    -   WPD at Idle; product valve is closed.    -   WPD at Standby; product valve is open.    -   WPD producing normal temperature water; product valve is open.    -   WPD awaiting filter replacement; product valve is closed.    -   WPD flushing lines and filter after filter replacement.    -   WPD producing hot water; produc; valve opens when at        temperature.    -   WPD disinfecting; product valve is closed.    -   WPD producing water sample for testing (eg. Chloramine testing);        product valve is closed.    -   WPD awaiting user entry in GUI to deliver water sample for        testing.    -   WPD is in a failsafe state; product valve is closed.

Preferably, the HDD controller commands the WPD to remain in Standbymode whenever it is not performing another operation. If it is inanother operation (for example, disinfecting) the HDD controller waitsfor this operation to be completed. Once the WPD is in Standby mode, theHDD controller may check to see if the WPD is due for a filter flushingoperation. If so, the WPD initiates a filter flush operation. The HDDmay also command a filter flush operation if, for example, there is apower interruption before a filter flush has been completed after filterreplacement.

Optionally, prior to the initiation of water production for a therapy,the HDD may be programmed to require the user to sample product waterfrom the WPD for various contaminants, such as chloramine. The HDD maycommand the WPD to initiate a water sampling state. When the WPDindicates a ready condition for sampling. The HDD then alerts the userto collect and test a water sample. If the user indicates that thesample has passed the test, the HDD may then command the WPD to beginwater production for a therapy. The HDD may optionally command the WPDinto a Standby state if the user indicates that the sample has failedthe test.

Errors originating from the WPD during water production can be signaledto the HHD, which may then send a command to acknowledge the errorcondition and issue an alert via an interface (e.g. the HDD interface)to the user. The WPD controller then waits for a command originatingfrom the user to either attempt to resume water production or totransition to a Standby state. A failsafe error condition wouldgenerally cease WPD operations and signal the HDD to initiate a therapytermination procedure.

1. A fluid-handling cassette assembly comprising: a middle cassetteinterposed between a first outer cassette and a second outer cassette;each said cassette comprising: a mid-plate positioned between a firstplate and a second plate, said plates having a length, a width and aplate thickness, a first side of the mid-plate opposing the first plateand a second side of the mid-pate opposing the second plate; the firstplate spaced apart from the mid-plate defining a width of a firstinter-plate space, and the second plate spaced apart from the mid-platedefining a width of a second inter-plate space; an edge of the cassettehaving a cassette thickness defined by the thickness of each plate plusthe width of the first and second inter-plate spaces, and a face of thecassette being defined by the length and width of the first or secondplate; a plurality of diaphragm valves or pumps comprising valve or pumpactuation chambers connected to actuation channels running parallel tothe face of the cassette within the first or second inter-plate space,and terminating in respective cassette valve or pump actuation ports ata first edge of the cassette between the first or second inter-platespace; and a fluid-handling pod positioned in an inter-cassette spacebetween the middle cassette and the first or second cassette; said podhaving a fluid connection to fluid channels in the middle, first orsecond cassette via a fluid conduit penetrating the face of the middle,first or second cassette; wherein the first edge of the middle, firstand second cassettes are located on a first side of the cassetteassembly, so that the cassette valve or pump actuation ports areconfigured to plug into or unplug from an actuation port receptacleassembly opposite the first side of the cassette assembly.
 2. Thecassette assembly of claim 1, wherein the fluid-handling pod comprises adiaphragm pump pod having an actuation and a fluid connection toactuation and fluid channels in the middle, first or second cassette viaan actuation conduit and a fluid conduit, each penetrating the face ofthe middle, first or second cassette.
 3. The cassette assembly of claim2, wherein the actuation conduit of the diaphragm pump pod connects toan actuation channel in a first or second inter-plate space of saidmiddle, first or second cassette, and has an uninterrupted connection toa cassette actuation port for the diaphragm pump pod on the first edgeof said middle, first or second cassette.
 4. The cassette assembly ofclaim 2, wherein the fluid conduit of the diaphragm pump pod connects toa fluid channel in a first or second inter-plate space of said middle,first or second cassette, and connects with a diaphragm valve in saidcassette, and wherein an actuation channel of said diaphragm valveconnects to a cassette actuation port for said diaphragm valve in thefirst edge of said middle, first or second cassette.
 5. The cassetteassembly of claim 1, wherein the fluid conduit is rigid.
 6. The cassetteassembly of claim 5, comprising a plurality of fluid-handling podsbetween the middle cassette and the first cassette, and between themiddle cassette and the second cassette, and wherein associated fluidconduits of this plurality of fluid-handling pods are rigid and providestructural support for the cassette assembly.
 7. The cassette assemblyof claim 1, comprising a cassette assembly frame configured to enhancethe structural stiffness of the cassette assembly, the cassette assemblyframe comprising a rigid support plate on a second side of the cassetteassembly opposite the first side of the cassette assembly, said supportplate configured to engage a cassette loading apparatus opposite theactuation port receptacle.
 8. A fluid-handling cassette assemblycomprising: a middle cassette interposed between a first outer cassetteand a second outer cassette; each said cassette comprising: a mid-platepositioned between a first plate and a second plate, said plates havinga length, a width and a plate thickness, a first side of the mid-plateopposing the first plate and a second side of the mid-pate opposing thesecond plate; the first plate spaced apart from the mid-plate defining awidth of a first inter-plate space, and the second plate spaced apartfrom the mid-plate defining a width of a second inter-plate space; anedge of the cassette having a cassette thickness defined by thethickness of each plate plus the width of the first and secondinter-plate spaces, and a face of the cassette being defined by thelength and width of the first or second plate; a plurality of diaphragmvalves or pumps comprising valve or pump actuation chambers connected toactuation channels running parallel to the face of the cassette withinthe first or second inter-plate space, and terminating in respectivecassette valve or pump actuation ports at a first edge of the cassettebetween the first or second inter-plate space; a first fluid-handlingpod positioned in an inter-cassette space between the middle cassetteand the first or second cassette; said pod having a fluid connection tofluid channels in the middle, first or second cassette via a fluidconduit penetrating the face of the middle, first or second cassette;and a second fluid-handling pod comprising a diaphragm pump pod havingan actuation and a fluid connection to actuation and fluid channels inthe middle, first or second cassette via an actuation conduit and afluid conduit, each penetrating the face of the middle, first or secondcassette; wherein the first edge of the middle, first and secondcassettes are located on a first side of the cassette assembly, so thatthe cassette valve or pump actuation ports are configured to plug intoor unplug from an actuation port receptacle assembly opposite the firstside of the cassette assembly.
 9. The cassette assembly of claim 8,wherein the actuation conduit of the diaphragm pump pod connects to anactuation channel in a first or second inter-plate space of said middle,first or second cassette, and has an uninterrupted connection to acassette actuation port for the diaphragm pump pod on the first edge ofsaid middle, first or second cassette.
 10. The cassette assembly ofclaim 8, wherein the fluid conduit of the diaphragm pump pod connects toa fluid channel in a first or second inter-plate space of said middle,first or second cassette, and connects with a diaphragm valve in saidcassette, and wherein an actuation channel of said diaphragm valveconnects to a cassette actuation port for said diaphragm valve in thefirst edge of said middle, first or second cassette.
 11. The cassetteassembly of claim 8, wherein the fluid conduit is rigid.
 12. Thecassette assembly of claim 11, comprising a plurality of fluid-handlingpods between the middle cassette and the first cassette, and between themiddle cassette and the second cassette, and wherein associated fluidconduits of this plurality of fluid-handling pods are rigid, providingstructural support for the cassette assembly.
 13. The cassette assemblyof claim 8, comprising a cassette assembly frame configured to enhancethe structural stiffness of the cassette assembly, the cassette assemblyframe comprising a rigid support plate on a second side of the cassetteassembly opposite the first side of the cassette assembly, said supportplate configured to engage a cassette loading apparatus opposite theactuation port receptacle.
 14. A fluid handling cassette comprising amid-plate positioned between a first plate and a second plate, saidplates having a length, a width and a plate thickness, a first side ofthe mid-plate opposing the first plate and a second side of the mid-pateopposing the second plate; the first plate spaced apart from themid-plate defining a width of a first inter-plate space, and the secondplate spaced apart from the mid-plate defining a width of a secondinter-plate space; an edge of the cassette having a cassette thicknessdefined by the thickness of each plate plus the width of the first andsecond inter-plate spaces, and a face of the cassette being defined bythe length and width of the first or second plate; the mid-platecomprising a pump station defined by a pump diaphragm and the first sideof the mid-plate, said pump diaphragm seated against the first side ofthe midplate and having an excursion range defined by the width of thefirst inter-plate space; and a pump actuation channel running parallelto the face of the cassette in the first inter-plate space connecting apump actuation chamber bounded by the first plate and the pump diaphragmwith a cassette pump actuation port located within the first inter-platespace at a first edge of the cassette.
 15. The cassette of claim 14,comprising a first and a second pump fluid port in the pump stationfluidly connecting a respective first and second fluid channel in thesecond inter-plate space to a pumping chamber defined by the pumpdiaphragm and the first side of the mid-plate.
 16. The cassette of claim14, comprising a pump fluid port in the pump station fluidly connectinga fluid channel in the second inter-plate space with a pumping chamberdefined by the pump diaphragm and the first side of the mid-plate. 17.The cassette of claim 14, comprising an aperture in the mid-plate at thepump station, said aperture allowing the pump diaphragm to move from thefirst plate to the second plate when actuated by positive or negativepressure delivered through the pump actuation channel.
 18. The cassetteof claim 14, wherein the plates are insufficiently thick to allow fluidor actuation channels to travel within the plates in a directionparallel to the face of the cassette.
 19. The cassette of claim 14,comprising a fluid channel running in the second inter-plate space, andfluidly connected to a pumping chamber defined by the pump diaphragm andthe first side of the mid-plate, said connection being made through oneor more pump fluid ports in the mid-plate, wherein the fluid channelruns parallel to the face of the cassette in the second inter-platespace connecting the pumping chamber with a cassette fluid port locatedwithin the second inter-plate space at the first edge or at a secondedge of the cassette.
 20. A fluid handling cassette comprising amid-plate positioned between a first plate and a second plate, saidplates having a length, a width and a plate thickness, a first side ofthe mid-plate opposing the first plate and a second side of the mid-pateopposing the second plate; the first plate spaced apart from themid-plate defining a width of a first inter-plate space, and the secondplate spaced apart from the mid-plate defining a width of a secondinter-plate space; an edge of the cassette having a cassette thicknessdefined by the thickness of each plate plus the width of the first andsecond inter-plate spaces, and a face of the cassette being defined bythe length and width of the first or second plate; the mid-platecomprising a valve station defined by a valve diaphragm and the firstside of the mid-plate, said valve diaphragm seated against the firstside of the midplate and having an excursion range defined by the widthof the first inter-plate space; and a valve actuation channel runningparallel to the face of the cassette in the first inter-plate spaceconnecting a valve actuation chamber bounded by the first plate and thevalve diaphragm with a cassette valve actuation port located within thefirst inter-plate space at a first edge of the cassette.
 21. Thecassette of claim 20, comprising a first and second valve fluid port inthe valve station fluidly connecting a respective first and second fluidchannel in the second inter-plate space to a valve fluid chamber definedby the valve diaphragm and the first side of the mid-plate.
 22. Thecassette of claim 21, wherein one or both valve fluid ports comprise araised valve seat to seal the valve diaphragm over the first or secondvalve fluid port when positive pressure is applied to the valvediaphragm via the valve actuation channel.
 23. The cassette of claim 21,wherein the first fluid channel is fluidically isolated from the secondfluid channel other than through the first and second valve fluid ports.24. The cassette of claim 20, comprising a fluid channel running in thesecond inter-plate space, and fluidly connected to a valve fluid chamberdefined by the valve diaphragm and the first side of the mid-plate, saidconnection being made through two valve fluid ports in the mid-plate,wherein the fluid channel runs parallel to the face of the cassette inthe second inter-plate space connecting the valve fluid chamber with acassette fluid port located within the second inter-plate space at thefirst edge or at a second edge of the cassette.
 25. A fluid handlingcassette comprising a mid-plate positioned between a first plate and asecond plate, said plates having a length, a width and a platethickness, a first side of the mid-plate opposing the first plate and asecond side of the mid-pate opposing the second plate; the first platespaced apart from the mid-plate defining a width of a first inter-platespace, and the second plate spaced apart from the mid-plate defining awidth of a second inter-plate space; an edge of the cassette having acassette thickness defined by the thickness of each plate plus the widthof the first and second inter-plate spaces, and a face of the cassettebeing defined by the length and width of the first or second plate; themid-plate comprising a pump station defined by a pump diaphragm and thefirst side of the mid-plate, said pump diaphragm seated against thefirst side of the mid-plate and having an excursion ranged defined bythe width of the first inter-plate space; the mid-plate also comprisingfirst and second valve stations, each defined by a valve diaphragm andthe first side of the mid-plate, said valve diaphragm seated against thefirst side of the midplate and having an excursion range defined by thewidth of the first inter-plate space; and a pump actuation channel forthe pump station, and a valve actuation channel for each of the firstand second valve stations; said pump actuation channel running parallelto the face of the cassette in the first inter-plate space connecting apump actuation chamber bounded by the first plate and the pump diaphragmwith a cassette pump actuation port located within the first inter-platespace at a first edge of the cassette; and each said valve actuationchannel running parallel to the face of the cassette in the firstinter-plate space connecting a valve actuation chamber bounded by thefirst plate and the valve diaphragm with a cassette valve actuation portlocated within the first inter-plate space at the first edge of thecassette.
 26. The cassette of claim 25, comprising an inlet and outletvalve fluid port in each of said two valve stations, and one or morepump fluid ports in the pump station, each of said valve and pump fluidports fluidly connecting a fluid channel in the second inter-plate spacewith: a pumping chamber defined by the pump diaphragm and the first sideof the mid-plate; and a valve fluid chamber in each of said valvestations defined by the corresponding valve diaphragm and the first sideof the mid-plate; the fluid channel having a flowpath that passesthrough said inlet and outlet valve fluid ports and said one or morepump fluid ports; wherein selective actuation of the pump actuationchamber and said valve actuation chambers allows for uni-directionalflow of a fluid through the fluid channel.
 27. The cassette of claim 25,comprising a fluid channel running in the second inter-plate space, andfluidly connected to: a pumping chamber defined by the pump diaphragmand the first side of the mid-plate, said connection being made througha pump fluid port in the mid-plate; and a valve fluid chamber of eachvalve station, each said valve fluid chamber being defined by thecorresponding valve diaphragm and the first side of the mid-plate, eachsaid connection being made through two valve fluid ports in themid-plate; wherein the fluid channel runs parallel to the face of thecassette in the second inter-plate space connecting the pumping chamberand each of the valve fluid chambers with a cassette fluid inlet portand a cassette fluid outlet port located within the second inter-platespace at the first edge or at a second edge of the cassette.
 28. Thecassette of claim 27, wherein the cassette fluid inlet port and cassettefluid outlet port are located at a second edge of the cassette, so thatthe cassette pump actuation port and the cassette valve actuation portare configured to be plugged directly into a mating actuation receptacleexternal to the cassette, and so that the fluid inlet port and fluidoutlet port are arranged to be connected via flexible or malleabletubing to a fluid source or destination external to the cassette. 29.The cassette of claim 25, comprising a fluid channel running in thesecond inter-plate space, and fluidly connected to: a pumping chamberdefined by the pump diaphragm and the first side of the mid-plate, saidconnection being made through a pump fluid port in the mid-plate; and avalve fluid chamber of each valve station, each said valve fluid chamberbeing defined by the corresponding valve diaphragm and the first side ofthe mid-plate, each said connection being made through two valve fluidports in the mid-plate; wherein the fluid channel runs parallel to theface of the cassette in the second inter-plate space and connects thepumping chamber and each of the valve fluid chambers with a cassettefluid inlet port and a cassette fluid outlet port, said cassette fluidinlet port and fluid outlet port exiting the cassette through rigidconduits originating on the mid-plate and penetrating the face of thecassette through the first or second outer plates.
 30. The cassette ofclaim 14 comprising a plurality of walls formed on the first and secondsides of the mid-plate, said walls arranged to be fused with the firstand second plates to form said actuation or fluid channels within thecassette.
 31. The cassette of claim 30, wherein a first type of saidwalls comprises parallel walls to define the actuation or fluidchannels, and a second type of said walls comprises circumferentialperimeter walls defining pump or valve actuation stations, and a thirdtype of said walls comprises adjacent end walls defining a channeltermination at which a valve or pump fluid port penetrates themid-plate.
 32. The cassette of claim 31, wherein the first platecomprises one or more circumferential valve or pump diaphragm retainersconfigured to fit within the circumferential perimeter walls of theopposing mid-plate that define pump or valve actuation stations, saidretainers arranged to clamp a peripheral bead or rim of an associateddiaphragm positioned in the pump or valve station of the mid-plate. 33.The cassette of claim 32, wherein the retainers include holes,fenestrations or slots to permit transmission of actuation fluid or gasbetween the valve or pump actuation chamber surrounded by the retainerand an associated actuation channel.
 34. The cassette of claim 31,wherein the first plate comprises an elongate rib configured to bepositioned within a mating actuation channel of the mid-plate, thecross-sectional size and length of the rib arranged to adjust theactuation channel volume to a pre-determined value between an actuationport of the cassette and an associated valve or pump actuation chamber.35. A fluid handling cassette comprising a mid-plate positioned betweena first plate and a second plate, said plates having a length, a widthand a plate thickness, a first side of the mid-plate opposing the firstplate and a second side of the mid-pate opposing the second plate; thefirst plate spaced apart from the mid-plate defining a width of a firstinter-plate space, and the second plate spaced apart from the mid-platedefining a width of a second inter-plate space; an edge of the cassettehaving a cassette thickness defined by the thickness of each plate plusthe width of the first and second inter-plate spaces, and a face of thecassette being defined by the length and width of the first or secondplate; the mid-plate comprising first and second valve stations, thefirst valve station defined by a first valve diaphragm and the firstside of the mid-plate, and the second valve station defined by a secondvalve diaphragm and the second side of the mid-plate, said first valvediaphragm seated against the first side of the midplate and having anexcursion range defined by the width of the first inter-plate space, andsaid second valve diaphragm seated against the second side of themid-plate and having an excursion range defined by the width of thesecond inter-plate space; and a first valve actuation channel for thefirst valve station and running parallel to the face of the cassette inthe first inter-plate space, and a second valve actuation channel forthe second valve station and running parallel to the face of thecassette in the second inter-plate space; said first valve actuationchannel connecting a first valve actuation chamber bounded by the firstplate and the first valve diaphragm with a first cassette valveactuation port located within the first inter-plate space at a firstedge of the cassette; and said second valve actuation channel connectinga second valve actuation chamber bounded by the second plate and thesecond valve diaphragm with a second cassette valve actuation portlocated within the second inter-plate space at the first edge of thecassette.
 36. A fluid handling cassette comprising a mid-platepositioned between a first plate and a second plate, said plates havinga length, a width and a plate thickness, a first side of the mid-plateopposing the first plate and a second side of the mid-pate opposing thesecond plate; the first plate spaced apart from the mid-plate defining awidth of a first inter-plate space, and the second plate spaced apartfrom the mid-plate defining a width of a second inter-plate space; anedge of the cassette having a cassette thickness defined by thethickness of each plate plus the width of the first and secondinter-plate spaces, and a face of the cassette being defined by thelength and width of the first or second plate; the mid-plate comprisingfirst and second pump stations, the first pump station defined by afirst pump diaphragm and the first side of the mid-plate, and the secondpump station defined by a second pump diaphragm and the second side ofthe mid-plate, said first pump diaphragm seated against the first sideof the midplate and having an excursion range defined by the width ofthe first inter-plate space, and said second pump diaphragm seatedagainst the second side of the mid-plate and having an excursion rangedefined by the width of the second inter-plate space; and a first pumpactuation channel for the first pump station and running parallel to theface of the cassette in the first inter-plate space, and a second pumpactuation channel for the second pump station and running parallel tothe face of the cassette in the second inter-plate space; said firstpump actuation channel connecting a first pump actuation chamber boundedby the first plate and the first pump diaphragm with a first cassettepump actuation port located within the first inter-plate space at afirst edge of the cassette; and said second pump actuation channelconnecting a second pump actuation chamber bounded by the second plateand the second pump diaphragm with a second cassette pump actuation portlocated within the second inter-plate space at the first edge of thecassette. 37.-59. (canceled)